Faculty Bibliography

Recent work identifies TMBIM5 as inner mitochondrial membrane Ca²⁺ /H⁺ exchanger, linking hyperpolarisation regulation to proteome control and energy metabolism.

Transesophageal echocardiography (TEE) use has become widespread in cardiac surgical operating rooms over the last 2 decades. Surgical and medical decision-making often are guided by the findings of the TEE examination, rendering TEE an invaluable tool both inside and outside the operating room. TEE has become ubiquitous in some parts because it is considered safe and relatively noninvasive. However, it is imperative for clinicians to understand that TEE can cause severe and possibly life-threatening complications, and the risks of TEE must be balanced against its benefits as a diagnostic tool. Upper gastrointestinal (UGI) injuries are the most commonly described complications of TEE; however, the relative infrequency of injuries and lack of uniform reporting make it difficult to definitively identify potential risk factors. Some large retrospective trials suggested that patient factors (age, body mass index, anatomic abnormalities), comorbid conditions (previous stroke), and procedural variables (procedure time, cardiopulmonary bypass time, etc.) are associated with TEE-related injuries. In this narrative review of complications from TEE, the authors focus on the incidence of UGI injuries, the spectrum of injuries associated with TEE, risk factors that may contribute to UGI injuries, as well as diagnosis and management options. Lastly, the discussion focuses on the prevention of injuries as TEE use continues to become more prevalent.

Chronic mitral regurgitation leads to a series of downstream pathologic changes, including pulmonary hypertension, right ventricular dilation, tricuspid leaflet tethering, and tricuspid annular dilation, which can result in functional tricuspid regurgitation (FTR). The five-year survival rate for patients with severe FTR is reported to be as low as 34%. While FTR was often left uncorrected during left-heart valvular surgery, under the assumption that correction of the left-sided lesion would reverse the right-heart changes that cause FTR, recent data largely have supported concomitant tricuspid valve repair at the time of mitral surgery. In this review, the authors discuss the potentially irreversible nature of the changes leading to FTR, the likelihood of progression of FTR after mitral surgery, and the evidence for and against concomitant tricuspid valve repair at the time of mitral valve intervention. Lastly, this narrative review also examines advances in transcatheter therapies for the tricuspid valve and the evidence behind concomitant transcatheter tricuspid repair at the time of transcatheter mitral repair.

Most mammalian phospholipids contain a saturated fatty acid at the sn-1 carbon atom and an unsaturated fatty acid at the sn-2 carbon atom of the glycerol backbone group. While the sn-2 linked chains undergo extensive remodeling by deacylation and reacylation (Lands cycle), it is not known how the composition of saturated fatty acids is controlled at the sn-1 position. Here, we demonstrate that lysophosphatidylglycerol acyltransferase 1 (LPGAT1) is an sn-1 specific acyltransferase that controls the stearate/palmitate ratio of phosphatidylethanolamine (PE) and phosphatidylcholine. Bacterially expressed murine LPGAT1 transferred saturated acyl-CoAs specifically into the sn-1 position of lysophosphatidylethanolamine (LPE) rather than lysophosphatidylglycerol and preferred stearoyl-CoA over palmitoyl-CoA as the substrate. In addition, genetic ablation of LPGAT1 in mice abolished 1-LPE:stearoyl-CoA acyltransferase activity and caused a shift from stearate to palmitate species in PE, dimethyl-PE, and phosphatidylcholine. Lysophosphatidylglycerol acyltransferase 1 KO mice were leaner and had a shorter life span than their littermate controls. Finally, we show that total lipid synthesis was reduced in isolated hepatocytes of LPGAT1 knockout mice. Thus, we conclude that LPGAT1 is an sn-1 specific LPE acyltransferase that controls the stearate/palmitate homeostasis of PE and the metabolites of the PE methylation pathway and that LPGAT1 plays a central role in the regulation of lipid biosynthesis with implications for body fat content and longevity.

This paper is the first of a four-part series that details the current barriers to diversity in the field of adult cardiothoracic anesthesiology and outlines actionable programs that can be implemented to create change. Part I and Part II address the training experience of women and underrepresented minorities (URMs) in adult cardiothoracic anesthesiology (ACTA), respectively, and explore concrete opportunities to promote positive change. Part III and Part IV examine the professional experience of URMs and women in ACTA, respectively, and discuss interventions that can facilitate a more equitable and inclusive environment for both groups. Although these problems are complex, the authors here offer a detailed analysis of the challenges faced by each group both in the training phase and the professional practice phase of their careers. The authors also present meaningful and concrete actions that can be implemented to create a more diverse, equitable, and inclusive professional environment in cardiovascular and thoracic anesthesiology.

Barth syndrome is a multisystem disorder caused by an abnormal metabolism of the mitochondrial lipid cardiolipin. In this review, we discuss physical properties, biosynthesis, membrane assembly, and function of cardiolipin. We hypothesize that cardiolipin reduces packing stress in the inner mitochondrial membrane, which arises as a result of protein crowding. According to this hypothesis, patients with Barth syndrome are unable to meet peak energy demands because they fail to concentrate the proteins of oxidative phosphorylation to a high surface density in the inner mitochondrial membrane.

Cardiolipin is known to interact with bacterial and mitochondrial proteins and protein complexes. Unlike in Escherichia coli and Saccharomyces cerevisiae, the synthesis of cardiolipin is essential for growth of Trypanosoma brucei parasites in culture. Inhibition of cardiolipin production has been shown to result in major changes in the T. brucei proteome and energy metabolism, with CLDP43, a mitochondrial protein containing a StaR-related lipid transfer (START)-like domain, being depleted in a cardiolipin-dependent way. We now show that in T. brucei procyclic forms lacking CLDP43, cardiolipin metabolism and mitochondrial function are affected. Using quantitative and qualitative lipid analyses, we found that while steady-state levels of cardiolipin were elevated in CLDP43 knock-out parasites compared to parental cells, de novo formation of cardiolipin was down-regulated. In addition, depletion of CLDP43 resulted in partial loss of mitochondrial membrane potential and decreased ATP production via substrate level phosphorylation. Recombinant CLDP43 was found to bind cardiolipin and phosphatidic acid in lipid overlay experiments, suggesting that it may be involved in transport or synthesis of cardiolipin or its precursors in T. brucei.

Mammalian spermatogenesis is associated with the transient appearance of condensed mitochondria, a singularity of germ cells with unknown function. Using proteomic analysis, respirometry, and electron microscopy with tomography, we studied the development of condensed mitochondria. Condensed mitochondria arose from orthodox mitochondria during meiosis by progressive contraction of the matrix space, which was accompanied by an initial expansion and a subsequent reduction of the surface area of the inner membrane. Compared to orthodox mitochondria, condensed mitochondria respired more actively, had a higher concentration of respiratory enzymes and supercomplexes, and contained more proteins involved in protein import and expression. After the completion of meiosis, the abundance of condensed mitochondria declined, which coincided with the onset of the biogenesis of acrosomes. Immuno-electron microscopy and the analysis of sub-cellular fractions suggested that condensed mitochondria or their fragments were translocated into the lumen of the acrosome. Thus, it seems condensed mitochondria are formed from orthodox mitochondria by extensive transformations in order to support the formation of the acrosomal matrix.