Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

Gottlieb, Roberta A.; Thomas, Amandine

doi:10.1007/s40139-017-0133-y

Cited by 39 publications

(39 citation statements)

References 105 publications

(127 reference statements)

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“…Mitochondria constitute 30% of the cardiomyocyte volume, and cardiomyocyte function is closely associated with mitochondrial activity. Consequently, mitochondrial dysfunction has been linked to heart dysfunction and remodeling (Pei et al, 2016;Gottlieb and Thomas, 2017). Our research group recently demonstrated complex mitochondrial alterations at the cardiomyocyte level of leptin-deficient obese mice (Stacchiotti et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

et al. 2020

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Integrative Physiology, a section of the journal Frontiers in PhysiologyObesity is a worldwide epidemic disease that induces important structural and functional changes to the heart and predisposes a patient to devastating cardiac complications. Sirtuin1 (SIRT1) has been found to have roles in regulating cardiac function, but whether it can help in cardioprotection is not clear. The aim of the present study was to determine whether melatonin, by modulating SIRT1 and in turn mitochondria signaling, may alleviate obesity-induced cardiac injuries. We investigated 10 lean control mice and 10 leptin-deficient obese mice (ob/ob) orally supplemented with melatonin for 8 weeks, as well as equal numbers of age-matched lean and ob/ob mice that did not receive melatonin. Hearts were evaluated using multiple parameters, including biometric values, morphology, SIRT1 activity and expression of markers of mitochondria biogenesis, oxidative stress, and inflammation. We observed that ob/ob mice experienced significant heart hypertrophy, infiltration by inflammatory cells, reduced SIRT1 activity, altered mitochondrial signaling and oxidative balance, and overexpression of inflammatory markers. Notably, melatonin supplementation in ob/ob mice reverted these obesogenic heart alterations. Melatonin prevented heart remodeling caused by obesity through SIRT1 activation, which, together with mitochondrial pathways, reduced oxidative stress and inflammation.Homogenized heart tissues were adequately processed for the quantitative measurement of natriuretic peptides type-B (BNP) protein level using a specific ELISA Kit (Novus Biologicals, Abingdon, United Kingdom), according to the manufacturer's Frontiers in Physiology | www.frontiersin.org

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Section: Introductionmentioning

confidence: 99%

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

et al. 2020

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“…Deficient response to oxidative stress can lead to inadequate removal of dysfunctional mitochondria and mitochondrial DNA, contributing to the inflammatory process. 46 , 47 Figure 2 represents the role of the hub genes identified and their possible contribution to inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

Rejection-associated Mitochondrial Impairment After Heart Transplantation

Romero

Chang

Tabak

et al. 2020

Transplantation Direct

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Background. Mitochondrial dysfunction is associated with poor allograft prognosis. Mitochondrial-related gene expression (GE) in endomyocardial biopsies (EMBs) could be useful as a nonimmune functional marker of rejection. We hypothesize that acute cardiac allograft rejection is associated with decreased mitochondrial-related GE in EMBs. Methods. We collected 64 routines or clinically indicated EMB from 47 patients after heart transplant. The EMBs were subjected to mRNA sequencing. We conducted weighted gene coexpression network analysis to construct module-derived eigengenes. The modules were assessed by gene ontology enrichment and hub gene analysis. Modules were correlated with the EMBs following the International Society of Heart and Lung Transplantation histology-based criteria and a classification based on GE alone; we also correlated with clinical parameters. Results. The modules enriched with mitochondria-related and immune-response genes showed the strongest correlation to the clinical traits. Compared with the no-rejection samples, rejection samples had a decreased activity of mitochondrial-related genes and an increased activity of immune-response genes. Biologic processes and hub genes in the mitochondria-related modules were primarily involved with energy generation, substrate metabolism, and regulation of oxidative stress. Compared with International Society of Heart and Lung Transplantation criteria, GE-based classification had stronger correlation to the weighted gene coexpression network analysis–derived functional modules. The brain natriuretic peptide level, ImmuKnow, and Allomap scores had negative relationships with the expression of mitochondria-related modules and positive relationships with immune-response modules. Conclusions. During acute cardiac allograft rejection, there was a decreased activity of mitochondrial-related genes, related to an increased activity of immune-response genes, and depressed allograft function manifested by brain natriuretic peptide elevation. This suggests a rejection-associated mitochondrial impairment.

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“…Mitophagy occurs through different pathways involving Parkin, BNIP3, or FUNDC1. These appear to be complementary and differentially activated according to the stimulus (2,3). Parkin-mediated mitophagy is generally triggered by mitochondrial inner membrane depolarization, which leads to PINK1 accumulation on the outer membrane and phosphorylation of targets that recruit Parkin.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, Parkin plays an important role in the heart's transition from fetal to postnatal life involving a metabolic switch from carbohydrates to fatty acids and amino acids for fuel utilization; this highlights its potential significance in metabolic remodeling of mitochondria (4). Related to that, obesity is known to induce metabolic reprogramming of mitochondria as well as mitochondrial dysfunction (3). However, little is known about the regulation of cardiac mitophagy in the context of obesity.…”

Section: Introductionmentioning

confidence: 99%

Decrease of Cardiac Parkin Protein in Obese Mice

Thomas

Marek-Iannucci

Tucker

et al. 2020

Front. Cardiovasc. Med.

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Mitophagy plays a major role in heart physiology. Impairment of Parkin-dependent mitophagy in heart is known to be deleterious. Obesity is a known cardiovascular risk factor. Impaired autophagy has been reported in models of obesity or hyperlipidemia/hypercholesterolemia; however less is known regarding obesity and mitophagy. The aim of this study was to evaluate the regulation of Parkin expression in hearts of mice fed a high fat diet. Interestingly, we found a significant decrease in Parkin protein in hearts of HFD mice compared those fed a low-fat diet. This was associated with mitochondrial dysfunction in the context of ischemia/reperfusion (I/R). This downregulation was not associated with a decrease in Parkin mRNA expression. We did not detect any change in the degradation rate of Parkin and only a slight decrease in its translation. The reduction of Parkin protein abundance in HFD hearts remains a mystery and will need further studies. However, Parkin depletion in the setting of obesity may contribute to cardiovascular risk.

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Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart

Cited by 39 publications

References 105 publications

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

RETRACTED: Sirtuin1 Role in the Melatonin Protective Effects Against Obesity-Related Heart Injury

Rejection-associated Mitochondrial Impairment After Heart Transplantation

Decrease of Cardiac Parkin Protein in Obese Mice

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