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130


Autophagy proteins control goblet cell function by potentiating reactive oxygen species production

Patel, Khushbu K; Miyoshi, Hiroyuki; Beatty, Wandy L; Head, Richard D; Malvin, Nicole P; Cadwell, Ken; Guan, Jun-Lin; Saitoh, Tatsuya; Akira, Shizuo; Seglen, Per O; Dinauer, Mary C; Virgin, Herbert W; Stappenbeck, Thaddeus S
Delivery of granule contents to epithelial surfaces by secretory cells is a critical physiologic process. In the intestine, goblet cells secrete mucus that is required for homeostasis. Autophagy proteins are required for secretion in some cases, though the mechanism and cell biological basis for this requirement remain unknown. We found that in colonic goblet cells, proteins involved in initiation and elongation of autophagosomes were required for efficient mucus secretion. The autophagy protein LC3 localized to intracellular multi-vesicular vacuoles that were consistent with a fusion of autophagosomes and endosomes. Using cultured intestinal epithelial cells, we found that NADPH oxidases localized to and enhanced the formation of these LC3-positive vacuoles. Both autophagy proteins and endosome formation were required for maximal production of reactive oxygen species (ROS) derived from NADPH oxidases. Importantly, generation of ROS was critical to control mucin granule accumulation in colonic goblet cells. Thus, autophagy proteins can control secretory function through ROS, which is in part generated by LC3-positive vacuole-associated NADPH oxidases. These findings provide a novel mechanism by which autophagy proteins can control secretion.
PMCID:3981139
PMID: 24185898
ISSN: 0261-4189
CID: 700592

Autophagy meets phagocytosis

Cadwell, Ken; Philips, Jennifer A
Autophagy can degrade intracellular bacteria, but how this pathway contributes to phagocytosis is unclear. In this issue of Immunity, Bonilla et al. (2013) demonstrate an additional role for autophagy in Mycobacterium tuberculosis internalization by macrophages.
PMID: 24054324
ISSN: 1074-7613
CID: 542812

A Deficiency in the Autophagy Gene Atg16L1 Enhances Resistance to Enteric Bacterial Infection

Marchiando, Amanda M; Ramanan, Deepshika; Ding, Yi; Gomez, Luis E; Hubbard-Lucey, Vanessa M; Maurer, Katie; Wang, Caihong; Ziel, Joshua W; van Rooijen, Nico; Nunez, Gabriel; Finlay, B Brett; Mysorekar, Indira U; Cadwell, Ken
Polymorphisms in the essential autophagy gene Atg16L1 have been linked with susceptibility to Crohn's disease, a major type of inflammatory bowel disease (IBD). Although the inability to control intestinal bacteria is thought to underlie IBD, the role of Atg16L1 during extracellular intestinal bacterial infections has not been sufficiently examined and compared to the function of other IBD susceptibility genes, such as Nod2, which encodes a cytosolic bacterial sensor. We find that Atg16L1 mutant mice are resistant to intestinal disease induced by the model bacterial pathogen Citrobacter rodentium. An Atg16L1 deficiency alters the intestinal environment to mediate an enhanced immune response that is dependent on monocytic cells, but this hyperimmune phenotype and its protective effects are lost in Atg16L1/Nod2 double-mutant mice. These results reveal an immunosuppressive function of Atg16L1 and suggest that gene variants affecting the autophagy pathway may have been evolutionarily maintained to protect against certain life-threatening infections.
PMCID:3825684
PMID: 23954160
ISSN: 1931-3128
CID: 503622

Bacteria, it's What's for Dinner

Cadwell, Ken
While intestinal epithelial cells are known for secreting antimicrobial molecules, cell intrinsic defense mechanisms are less characterized. In this issue, Benjamin et al. (2013) demonstrate that MyD88 and autophagy within the intestinal epithelium detect invasive bacteria and prevent dissemination.
PMCID:3034397
PMID: 23768486
ISSN: 1931-3128
CID: 394132

FIP200 regulates targeting of Atg16L1 to the isolation membrane

Nishimura, Taki; Kaizuka, Takeshi; Cadwell, Ken; Sahani, Mayurbhai H; Saitoh, Tatsuya; Akira, Shizuo; Virgin, Herbert W; Mizushima, Noboru
Autophagosome formation is a dynamic process that is strictly controlled by autophagy-related (Atg) proteins. However, how these Atg proteins are recruited to the autophagosome formation site or autophagic membranes remains poorly understood. Here, we found that FIP200, which is involved in proximal events, directly interacts with Atg16L1, one of the downstream Atg factors, in an Atg14- and phosphatidylinositol 3-kinase-independent manner. Atg16L1 deletion mutants, which lack the FIP200-interacting domain, are defective in proper membrane targeting. Thus, FIP200 regulates not only early events but also late events of autophagosome formation through direct interaction with Atg16L1.
PMCID:3589088
PMID: 23392225
ISSN: 1469-221x
CID: 232302

Atg16L1 deficiency confers protection from uropathogenic Escherichia coli infection in vivo

Wang, Caihong; Mendonsa, Graziella R; Symington, Jane W; Zhang, Qunyuan; Cadwell, Ken; Virgin, Herbert W; Mysorekar, Indira U
Urinary tract infection (UTI), a frequent and important disease in humans, is primarily caused by uropathogenic Escherichia coli (UPEC). UPEC forms acute cytoplasmic biofilms within superficial urothelial cells and can persist by establishing membrane-enclosed latent reservoirs to seed recurrent UTI. The host responds with an influx of innate immune cells and shedding of infected epithelial cells. The autophagy gene ATG16L1 has a commonly occurring mutation that is associated with inflammatory disease and intestinal cell abnormalities in mice and humans. Here, we show that Atg16L1-deficient mice (Atg16L1(HM)) cleared bacteriuria more rapidly and thoroughly than controls and showed rapid epithelial recovery. Atg16L1 deficiency was associated with a potent proinflammatory cytokine response with increased recruitment of monocytes and neutrophils to infected bladders. Chimeric and genetic studies showed that Atg16L1(HM) hematopoietic cells alone could increase clearance and that Atg16L1-deficient innate immune cells were required and sufficient for enhanced bacteriuric clearance. We also show that Atg16L1-deficient mice exhibit cell-autonomous architectural aberrations of superficial urothelial cells, including increases in multivesicular bodies, lysosomes, and expression of the UPEC receptor Up1a. Finally, we show that Atg16L1(HM) epithelial cells contained a significantly reduced number of latent reservoirs. Together, our results show that Atg16L1 deficiency confers protection in vivo to the host against both acute and latent UPEC infection, suggest that deficiency in a key autophagy protein can be protective against infection in an animal model of one of the most common diseases of women worldwide, and may have significant clinical implications for understanding the etiology of recurrent UTIs.
PMCID:3390880
PMID: 22715292
ISSN: 0027-8424
CID: 232312

Guidelines for the use and interpretation of assays for monitoring autophagy [Guideline]

Klionsky, Daniel J; Abdalla, Fabio C; Abeliovich, Hagai; Abraham, Robert T; Acevedo-Arozena, Abraham; Adeli, Khosrow; Agholme, Lotta; Agnello, Maria; Agostinis, Patrizia; Aguirre-Ghiso, Julio A; Ahn, Hyung Jun; Ait-Mohamed, Ouardia; Ait-Si-Ali, Slimane; Akematsu, Takahiko; Akira, Shizuo; Al-Younes, Hesham M; Al-Zeer, Munir A; Albert, Matthew L; Albin, Roger L; Alegre-Abarrategui, Javier; Aleo, Maria Francesca; Alirezaei, Mehrdad; Almasan, Alexandru; Almonte-Becerril, Maylin; Amano, Atsuo; Amaravadi, Ravi; Amarnath, Shoba; Amer, Amal O; Andrieu-Abadie, Nathalie; Anantharam, Vellareddy; Ann, David K; Anoopkumar-Dukie, Shailendra; Aoki, Hiroshi; Apostolova, Nadezda; Arancia, Giuseppe; Aris, John P; Asanuma, Katsuhiko; Asare, Nana Y O; Ashida, Hisashi; Askanas, Valerie; Askew, David S; Auberger, Patrick; Baba, Misuzu; Backues, Steven K; Baehrecke, Eric H; Bahr, Ben A; Bai, Xue-Yuan; Bailly, Yannick; Baiocchi, Robert; Baldini, Giulia; Balduini, Walter; Ballabio, Andrea; Bamber, Bruce A; Bampton, Edward T W; Banhegyi, Gabor; Bartholomew, Clinton R; Bassham, Diane C; Bast, Robert C Jr; Batoko, Henri; Bay, Boon-Huat; Beau, Isabelle; Bechet, Daniel M; Begley, Thomas J; Behl, Christian; Behrends, Christian; Bekri, Soumeya; Bellaire, Bryan; Bendall, Linda J; Benetti, Luca; Berliocchi, Laura; Bernardi, Henri; Bernassola, Francesca; Besteiro, Sebastien; Bhatia-Kissova, Ingrid; Bi, Xiaoning; Biard-Piechaczyk, Martine; Blum, Janice S; Boise, Lawrence H; Bonaldo, Paolo; Boone, David L; Bornhauser, Beat C; Bortoluci, Karina R; Bossis, Ioannis; Bost, Frederic; Bourquin, Jean-Pierre; Boya, Patricia; Boyer-Guittaut, Michael; Bozhkov, Peter V; Brady, Nathan R; Brancolini, Claudio; Brech, Andreas; Brenman, Jay E; Brennand, Ana; Bresnick, Emery H; Brest, Patrick; Bridges, Dave; Bristol, Molly L; Brookes, Paul S; Brown, Eric J; Brumell, John H; Brunetti-Pierri, Nicola; Brunk, Ulf T; Bulman, Dennis E; Bultman, Scott J; Bultynck, Geert; Burbulla, Lena F; Bursch, Wilfried; Butchar, Jonathan P; Buzgariu, Wanda; Bydlowski, Sergio P; Cadwell, Ken; Cahova, Monika; Cai, Dongsheng; Cai, Jiyang; Cai, Qian; Calabretta, Bruno; Calvo-Garrido, Javier; Camougrand, Nadine; Campanella, Michelangelo; Campos-Salinas, Jenny; Candi, Eleonora; Cao, Lizhi; Caplan, Allan B; Carding, Simon R; Cardoso, Sandra M; Carew, Jennifer S; Carlin, Cathleen R; Carmignac, Virginie; Carneiro, Leticia A M; Carra, Serena; Caruso, Rosario A; Casari, Giorgio; Casas, Caty; Castino, Roberta; Cebollero, Eduardo; Cecconi, Francesco; Celli, Jean; Chaachouay, Hassan; Chae, Han-Jung; Chai, Chee-Yin; Chan, David C; Chan, Edmond Y; Chang, Raymond Chuen-Chung; Che, Chi-Ming; Chen, Ching-Chow; Chen, Guang-Chao; Chen, Guo-Qiang; Chen, Min; Chen, Quan; Chen, Steve S-L; Chen, WenLi; Chen, Xi; Chen, Xiangmei; Chen, Xiequn; Chen, Ye-Guang; Chen, Yingyu; Chen, Yongqiang; Chen, Yu-Jen; Chen, Zhixiang; Cheng, Alan; Cheng, Christopher H K; Cheng, Yan; Cheong, Heesun; Cheong, Jae-Ho; Cherry, Sara; Chess-Williams, Russ; Cheung, Zelda H; Chevet, Eric; Chiang, Hui-Ling; Chiarelli, Roberto; Chiba, Tomoki; Chin, Lih-Shen; Chiou, Shih-Hwa; Chisari, Francis V; Cho, Chi Hin; Cho, Dong-Hyung; Choi, Augustine M K; Choi, DooSeok; Choi, Kyeong Sook; Choi, Mary E; Chouaib, Salem; Choubey, Divaker; Choubey, Vinay; Chu, Charleen T; Chuang, Tsung-Hsien; Chueh, Sheau-Huei; Chun, Taehoon; Chwae, Yong-Joon; Chye, Mee-Len; Ciarcia, Roberto; Ciriolo, Maria R; Clague, Michael J; Clark, Robert S B; Clarke, Peter G H; Clarke, Robert; Codogno, Patrice; Coller, Hilary A; Colombo, Maria I; Comincini, Sergio; Condello, Maria; Condorelli, Fabrizio; Cookson, Mark R; Coombs, Graham H; Coppens, Isabelle; Corbalan, Ramon; Cossart, Pascale; Costelli, Paola; Costes, Safia; Coto-Montes, Ana; Couve, Eduardo; Coxon, Fraser P; Cregg, James M; Crespo, Jose L; Cronje, Marianne J; Cuervo, Ana Maria; Cullen, Joseph J; Czaja, Mark J; D'Amelio, Marcello; Darfeuille-Michaud, Arlette; Davids, Lester M; Davies, Faith E; De Felici, Massimo; de Groot, John F; de Haan, Cornelis A M; De Martino, Luisa; De Milito, Angelo; De Tata, Vincenzo; Debnath, Jayanta; Degterev, Alexei; Dehay, Benjamin; Delbridge, Lea M D; Demarchi, Francesca; Deng, Yi Zhen; Dengjel, Jorn; Dent, Paul; Denton, Donna; Deretic, Vojo; Desai, Shyamal D; Devenish, Rodney J; Di Gioacchino, Mario; Di Paolo, Gilbert; Di Pietro, Chiara; Diaz-Araya, Guillermo; Diaz-Laviada, Ines; Diaz-Meco, Maria T; Diaz-Nido, Javier; Dikic, Ivan; Dinesh-Kumar, Savithramma P; Ding, Wen-Xing; Distelhorst, Clark W; Diwan, Abhinav; Djavaheri-Mergny, Mojgan; Dokudovskaya, Svetlana; Dong, Zheng; Dorsey, Frank C; Dosenko, Victor; Dowling, James J; Doxsey, Stephen; Dreux, Marlene; Drew, Mark E; Duan, Qiuhong; Duchosal, Michel A; Duff, Karen; Dugail, Isabelle; Durbeej, Madeleine; Duszenko, Michael; Edelstein, Charles L; Edinger, Aimee L; Egea, Gustavo; Eichinger, Ludwig; Eissa, N Tony; Ekmekcioglu, Suhendan; El-Deiry, Wafik S; Elazar, Zvulun; Elgendy, Mohamed; Ellerby, Lisa M; Eng, Kai Er; Engelbrecht, Anna-Mart; Engelender, Simone; Erenpreisa, Jekaterina; Escalante, Ricardo; Esclatine, Audrey; Eskelinen, Eeva-Liisa; Espert, Lucile; Espina, Virginia; Fan, Huizhou; Fan, Jia; Fan, Qi-Wen; Fan, Zhen; Fang, Shengyun; Fang, Yongqi; Fanto, Manolis; Fanzani, Alessandro; Farkas, Thomas; Farre, Jean-Claude; Faure, Mathias; Fechheimer, Marcus; Feng, Carl G; Feng, Jian; Feng, Qili; Feng, Youji; Fesus, Laszlo; Feuer, Ralph; Figueiredo-Pereira, Maria E; Fimia, Gian Maria; Fingar, Diane C; Finkbeiner, Steven; Finkel, Toren; Finley, Kim D; Fiorito, Filomena; Fisher, Edward A; Fisher, Paul B; Flajolet, Marc; Florez-McClure, Maria L; Florio, Salvatore; Fon, Edward A; Fornai, Francesco; Fortunato, Franco; Fotedar, Rati; Fowler, Daniel H; Fox, Howard S; Franco, Rodrigo; Frankel, Lisa B; Fransen, Marc; Fuentes, Jose M; Fueyo, Juan; Fujii, Jun; Fujisaki, Kozo; Fujita, Eriko; Fukuda, Mitsunori; Furukawa, Ruth H; Gaestel, Matthias; Gailly, Philippe; Gajewska, Malgorzata; Galliot, Brigitte; Galy, Vincent; Ganesh, Subramaniam; Ganetzky, Barry; Ganley, Ian G; Gao, Fen-Biao; Gao, George F; Gao, Jinming; Garcia, Lorena; Garcia-Manero, Guillermo; Garcia-Marcos, Mikel; Garmyn, Marjan; Gartel, Andrei L; Gatti, Evelina; Gautel, Mathias; Gawriluk, Thomas R; Gegg, Matthew E; Geng, Jiefei; Germain, Marc; Gestwicki, Jason E; Gewirtz, David A; Ghavami, Saeid; Ghosh, Pradipta; Giammarioli, Anna M; Giatromanolaki, Alexandra N; Gibson, Spencer B; Gilkerson, Robert W; Ginger, Michael L; Ginsberg, Henry N; Golab, Jakub; Goligorsky, Michael S; Golstein, Pierre; Gomez-Manzano, Candelaria; Goncu, Ebru; Gongora, Celine; Gonzalez, Claudio D; Gonzalez, Ramon; Gonzalez-Estevez, Cristina; Gonzalez-Polo, Rosa Ana; Gonzalez-Rey, Elena; Gorbunov, Nikolai V; Gorski, Sharon; Goruppi, Sandro; Gottlieb, Roberta A; Gozuacik, Devrim; Granato, Giovanna Elvira; Grant, Gary D; Green, Kim N; Gregorc, Ales; Gros, Frederic; Grose, Charles; Grunt, Thomas W; Gual, Philippe; Guan, Jun-Lin; Guan, Kun-Liang; Guichard, Sylvie M; Gukovskaya, Anna S; Gukovsky, Ilya; Gunst, Jan; Gustafsson, Asa B; Halayko, Andrew J; Hale, Amber N; Halonen, Sandra K; Hamasaki, Maho; Han, Feng; Han, Ting; Hancock, Michael K; Hansen, Malene; Harada, Hisashi; Harada, Masaru; Hardt, Stefan E; Harper, J Wade; Harris, Adrian L; Harris, James; Harris, Steven D; Hashimoto, Makoto; Haspel, Jeffrey A; Hayashi, Shin-ichiro; Hazelhurst, Lori A; He, Congcong; He, You-Wen; Hebert, Marie-Josee; Heidenreich, Kim A; Helfrich, Miep H; Helgason, Gudmundur V; Henske, Elizabeth P; Herman, Brian; Herman, Paul K; Hetz, Claudio; Hilfiker, Sabine; Hill, Joseph A; Hocking, Lynne J; Hofman, Paul; Hofmann, Thomas G; Hohfeld, Jorg; Holyoake, Tessa L; Hong, Ming-Huang; Hood, David A; Hotamisligil, Gokhan S; Houwerzijl, Ewout J; Hoyer-Hansen, Maria; Hu, Bingren; Hu, Chien-An A; Hu, Hong-Ming; Hua, Ya; Huang, Canhua; Huang, Ju; Huang, Shengbing; Huang, Wei-Pang; Huber, Tobias B; Huh, Won-Ki; Hung, Tai-Ho; Hupp, Ted R; Hur, Gang Min; Hurley, James B; Hussain, Sabah N A; Hussey, Patrick J; Hwang, Jung Jin; Hwang, Seungmin; Ichihara, Atsuhiro; Ilkhanizadeh, Shirin; Inoki, Ken; Into, Takeshi; Iovane, Valentina; Iovanna, Juan L; Ip, Nancy Y; Isaka, Yoshitaka; Ishida, Hiroyuki; Isidoro, Ciro; Isobe, Ken-ichi; Iwasaki, Akiko; Izquierdo, Marta; Izumi, Yotaro; Jaakkola, Panu M; Jaattela, Marja; Jackson, George R; Jackson, William T; Janji, Bassam; Jendrach, Marina; Jeon, Ju-Hong; Jeung, Eui-Bae; Jiang, Hong; Jiang, Hongchi; Jiang, Jean X; Jiang, Ming; Jiang, Qing; Jiang, Xuejun; Jiang, Xuejun; Jimenez, Alberto; Jin, Meiyan; Jin, Shengkan; Joe, Cheol O; Johansen, Terje; Johnson, Daniel E; Johnson, Gail V W; Jones, Nicola L; Joseph, Bertrand; Joseph, Suresh K; Joubert, Annie M; Juhasz, Gabor; Juillerat-Jeanneret, Lucienne; Jung, Chang Hwa; Jung, Yong-Keun; Kaarniranta, Kai; Kaasik, Allen; Kabuta, Tomohiro; Kadowaki, Motoni; Kagedal, Katarina; Kamada, Yoshiaki; Kaminskyy, Vitaliy O; Kampinga, Harm H; Kanamori, Hiromitsu; Kang, Chanhee; Kang, Khong Bee; Kang, Kwang Il; Kang, Rui; Kang, Yoon-A; Kanki, Tomotake; Kanneganti, Thirumala-Devi; Kanno, Haruo; Kanthasamy, Anumantha G; Kanthasamy, Arthi; Karantza, Vassiliki; Kaushal, Gur P; Kaushik, Susmita; Kawazoe, Yoshinori; Ke, Po-Yuan; Kehrl, John H; Kelekar, Ameeta; Kerkhoff, Claus; Kessel, David H; Khalil, Hany; Kiel, Jan A K W; Kiger, Amy A; Kihara, Akio; Kim, Deok Ryong; Kim, Do-Hyung; Kim, Dong-Hou; Kim, Eun-Kyoung; Kim, Hyung-Ryong; Kim, Jae-Sung; Kim, Jeong Hun; Kim, Jin Cheon; Kim, John K; Kim, Peter K; Kim, Seong Who; Kim, Yong-Sun; Kim, Yonghyun; Kimchi, Adi; Kimmelman, Alec C; King, Jason S; Kinsella, Timothy J; Kirkin, Vladimir; Kirshenbaum, Lorrie A; Kitamoto, Katsuhiko; Kitazato, Kaio; Klein, Ludger; Klimecki, Walter T; Klucken, Jochen; Knecht, Erwin; Ko, Ben C B; Koch, Jan C; Koga, Hiroshi; Koh, Jae-Young; Koh, Young Ho; Koike, Masato; Komatsu, Masaaki; Kominami, Eiki; Kong, Hee Jeong; Kong, Wei-Jia; Korolchuk, Viktor I; Kotake, Yaichiro; Koukourakis, Michael I; Kouri Flores, Juan B; Kovacs, Attila L; Kraft, Claudine; Krainc, Dimitri; Kramer, Helmut; Kretz-Remy, Carole; Krichevsky, Anna M; Kroemer, Guido; Kruger, Rejko; Krut, Oleg; Ktistakis, Nicholas T; Kuan, Chia-Yi; Kucharczyk, Roza; Kumar, Ashok; Kumar, Raj; Kumar, Sharad; Kundu, Mondira; Kung, Hsing-Jien; Kurz, Tino; Kwon, Ho Jeong; La Spada, Albert R; Lafont, Frank; Lamark, Trond; Landry, Jacques; Lane, Jon D; Lapaquette, Pierre; Laporte, Jocelyn F; Laszlo, Lajos; Lavandero, Sergio; Lavoie, Josee N; Layfield, Robert; Lazo, Pedro A; Le, Weidong; Le Cam, Laurent; Ledbetter, Daniel J; Lee, Alvin J X; Lee, Byung-Wan; Lee, Gyun Min; Lee, Jongdae; Lee, Ju-Hyun; Lee, Michael; Lee, Myung-Shik; Lee, Sug Hyung; Leeuwenburgh, Christiaan; Legembre, Patrick; Legouis, Renaud; Lehmann, Michael; Lei, Huan-Yao; Lei, Qun-Ying; Leib, David A; Leiro, Jose; Lemasters, John J; Lemoine, Antoinette; Lesniak, Maciej S; Lev, Dina; Levenson, Victor V; Levine, Beth; Levy, Efrat; Li, Faqiang; Li, Jun-Lin; Li, Lian; Li, Sheng; Li, Weijie; Li, Xue-Jun; Li, Yan-bo; Li, Yi-Ping; Liang, Chengyu; Liang, Qiangrong; Liao, Yung-Feng; Liberski, Pawel P; Lieberman, Andrew; Lim, Hyunjung J; Lim, Kah-Leong; Lim, Kyu; Lin, Chiou-Feng; Lin, Fu-Cheng; Lin, Jian; Lin, Jiandie D; Lin, Kui; Lin, Wan-Wan; Lin, Weei-Chin; Lin, Yi-Ling; Linden, Rafael; Lingor, Paul; Lippincott-Schwartz, Jennifer; Lisanti, Michael P; Liton, Paloma B; Liu, Bo; Liu, Chun-Feng; Liu, Kaiyu; Liu, Leyuan; Liu, Qiong A; Liu, Wei; Liu, Young-Chau; Liu, Yule; Lockshin, Richard A; Lok, Chun-Nam; Lonial, Sagar; Loos, Benjamin; Lopez-Berestein, Gabriel; Lopez-Otin, Carlos; Lossi, Laura; Lotze, Michael T; Low, Peter; Lu, Binfeng; Lu, Bingwei; Lu, Bo; Lu, Zhen; Luciano, Frederic; Lukacs, Nicholas W; Lund, Anders H; Lynch-Day, Melinda A; Ma, Yong; Macian, Fernando; MacKeigan, Jeff P; Macleod, Kay F; Madeo, Frank; Maiuri, Luigi; Maiuri, Maria Chiara; Malagoli, Davide; Malicdan, May Christine V; Malorni, Walter; Man, Na; Mandelkow, Eva-Maria; Manon, Stephen; Manov, Irena; Mao, Kai; Mao, Xiang; Mao, Zixu; Marambaud, Philippe; Marazziti, Daniela; Marcel, Yves L; Marchbank, Katie; Marchetti, Piero; Marciniak, Stefan J; Marcondes, Mateus; Mardi, Mohsen; Marfe, Gabriella; Marino, Guillermo; Markaki, Maria; Marten, Mark R; Martin, Seamus J; Martinand-Mari, Camille; Martinet, Wim; Martinez-Vicente, Marta; Masini, Matilde; Matarrese, Paola; Matsuo, Saburo; Matteoni, Raffaele; Mayer, Andreas; Mazure, Nathalie M; McConkey, David J; McConnell, Melanie J; McDermott, Catherine; McDonald, Christine; McInerney, Gerald M; McKenna, Sharon L; McLaughlin, BethAnn; McLean, Pamela J; McMaster, Christopher R; McQuibban, G Angus; Meijer, Alfred J; Meisler, Miriam H; Melendez, Alicia; Melia, Thomas J; Melino, Gerry; Mena, Maria A; Menendez, Javier A; Menna-Barreto, Rubem F S; Menon, Manoj B; Menzies, Fiona M; Mercer, Carol A; Merighi, Adalberto; Merry, Diane E; Meschini, Stefania; Meyer, Christian G; Meyer, Thomas F; Miao, Chao-Yu; Miao, Jun-Ying; Michels, Paul A M; Michiels, Carine; Mijaljica, Dalibor; Milojkovic, Ana; Minucci, Saverio; Miracco, Clelia; Miranti, Cindy K; Mitroulis, Ioannis; Miyazawa, Keisuke; Mizushima, Noboru; Mograbi, Baharia; Mohseni, Simin; Molero, Xavier; Mollereau, Bertrand; Mollinedo, Faustino; Momoi, Takashi; Monastyrska, Iryna; Monick, Martha M; Monteiro, Mervyn J; Moore, Michael N; Mora, Rodrigo; Moreau, Kevin; Moreira, Paula I; Moriyasu, Yuji; Moscat, Jorge; Mostowy, Serge; Mottram, Jeremy C; Motyl, Tomasz; Moussa, Charbel E-H; Muller, Sylke; Muller, Sylviane; Munger, Karl; Munz, Christian; Murphy, Leon O; Murphy, Maureen E; Musaro, Antonio; Mysorekar, Indira; Nagata, Eiichiro; Nagata, Kazuhiro; Nahimana, Aimable; Nair, Usha; Nakagawa, Toshiyuki; Nakahira, Kiichi; Nakano, Hiroyasu; Nakatogawa, Hitoshi; Nanjundan, Meera; Naqvi, Naweed I; Narendra, Derek P; Narita, Masashi; Navarro, Miguel; Nawrocki, Steffan T; Nazarko, Taras Y; Nemchenko, Andriy; Netea, Mihai G; Neufeld, Thomas P; Ney, Paul A; Nezis, Ioannis P; Nguyen, Huu Phuc; Nie, Daotai; Nishino, Ichizo; Nislow, Corey; Nixon, Ralph A; Noda, Takeshi; Noegel, Angelika A; Nogalska, Anna; Noguchi, Satoru; Notterpek, Lucia; Novak, Ivana; Nozaki, Tomoyoshi; Nukina, Nobuyuki; Nurnberger, Thorsten; Nyfeler, Beat; Obara, Keisuke; Oberley, Terry D; Oddo, Salvatore; Ogawa, Michinaga; Ohashi, Toya; Okamoto, Koji; Oleinick, Nancy L; Oliver, F Javier; Olsen, Laura J; Olsson, Stefan; Opota, Onya; Osborne, Timothy F; Ostrander, Gary K; Otsu, Kinya; Ou, Jing-hsiung James; Ouimet, Mireille; Overholtzer, Michael; Ozpolat, Bulent; Paganetti, Paolo; Pagnini, Ugo; Pallet, Nicolas; Palmer, Glen E; Palumbo, Camilla; Pan, Tianhong; Panaretakis, Theocharis; Pandey, Udai Bhan; Papackova, Zuzana; Papassideri, Issidora; Paris, Irmgard; Park, Junsoo; Park, Ohkmae K; Parys, Jan B; Parzych, Katherine R; Patschan, Susann; Patterson, Cam; Pattingre, Sophie; Pawelek, John M; Peng, Jianxin; Perlmutter, David H; Perrotta, Ida; Perry, George; Pervaiz, Shazib; Peter, Matthias; Peters, Godefridus J; Petersen, Morten; Petrovski, Goran; Phang, James M; Piacentini, Mauro; Pierre, Philippe; Pierrefite-Carle, Valerie; Pierron, Gerard; Pinkas-Kramarski, Ronit; Piras, Antonio; Piri, Natik; Platanias, Leonidas C; Poggeler, Stefanie; Poirot, Marc; Poletti, Angelo; Pous, Christian; Pozuelo-Rubio, Mercedes; Praetorius-Ibba, Mette; Prasad, Anil; Prescott, Mark; Priault, Muriel; Produit-Zengaffinen, Nathalie; Progulske-Fox, Ann; Proikas-Cezanne, Tassula; Przedborski, Serge; Przyklenk, Karin; Puertollano, Rosa; Puyal, Julien; Qian, Shu-Bing; Qin, Liang; Qin, Zheng-Hong; Quaggin, Susan E; Raben, Nina; Rabinowich, Hannah; Rabkin, Simon W; Rahman, Irfan; Rami, Abdelhaq; Ramm, Georg; Randall, Glenn; Randow, Felix; Rao, V Ashutosh; Rathmell, Jeffrey C; Ravikumar, Brinda; Ray, Swapan K; Reed, Bruce H; Reed, John C; Reggiori, Fulvio; Regnier-Vigouroux, Anne; Reichert, Andreas S; Reiners, John J Jr; Reiter, Russel J; Ren, Jun; Revuelta, Jose L; Rhodes, Christopher J; Ritis, Konstantinos; Rizzo, Elizete; Robbins, Jeffrey; Roberge, Michel; Roca, Hernan; Roccheri, Maria C; Rocchi, Stephane; Rodemann, H Peter; Rodriguez de Cordoba, Santiago; 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In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
PMCID:3404883
PMID: 22966490
ISSN: 1554-8627
CID: 181862

Viruses, autophagy genes, and Crohn's disease

Hubbard, Vanessa M; Cadwell, Ken
The etiology of the intestinal disease Crohn's disease involves genetic factors as well as ill-defined environmental agents. Several genetic variants linked to this disease are associated with autophagy, a process that is critical for proper responses to viral infections. While a role for viruses in this disease remains speculative, accumulating evidence indicate that this possibility requires serious consideration. In this review, we will examine the three-way relationship between viruses, autophagy genes, and Crohn's disease and discuss how host-pathogen interactions can mediate complex inflammatory disorders
PMCID:3185787
PMID: 21994779
ISSN: 1999-4915
CID: 150323

Crohn's disease susceptibility gene interactions, a NOD to the newcomer ATG16L1 [Comment]

Cadwell, Ken
PMID: 20875485
ISSN: 0016-5085
CID: 232322

Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters (vol 5, pg 511, 2009) [Correction]

Ju, Jeong-Sun; Miller, Sara E.; Jackson, Erin; Cadwell, Ken; Piwnica-Worms, David; Weihl, Conrad C.
ISI:000279429200022
ISSN: 1554-8627
CID: 3588712