Mitophagy and mitochondrial biogenesis in atrial tissue of patients undergoing heart surgery with cardiopulmonary bypass

Andres, Allen M.; Tucker, Kyle C.; Thomas, Amandine; Taylor, David J.; Sengstock, David; Jahania, Salik; Dabir, Reza; Pourpirali, Somayeh; Brown, Jamelle; Westbrook, David G.; Ballinger, Scott W.; Mentzer, Robert M.; Gottlieb, Roberta A.

doi:10.1172/jci.insight.89303

Cited by 57 publications

(49 citation statements)

References 28 publications

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“…Altered mitochondrial structure and/or function secondary to differences in sarcomere and myofibril architecture could be a missing piece of this puzzle. Furthermore, alterations in biogenesis, fusion, fission, and mitophagy are associated with cardiac differentiation and maturation (5,14,34) as well as many cardiac diseases (3,23,58,59). Thus characterizing mitochondrial fragmentation and turnover due to ECM elasticity and tissue architecture could provide mechanistic insight into some of our results.…”

Section: Discussionmentioning

confidence: 87%

“…cardiac myocytes; mitochondria; extracellular matrix; mechanotransduction; microfabrication BECAUSE OF THE SIGNIFICANT AMOUNT of energy required for sarcomere shortening, mitochondria are especially prevalent in cardiac myocytes, occupying~35% of cell volume (15,25). Mitochondria in cardiac myocytes remodel both structurally and functionally throughout development, health, and disease (2,3,23). For example, neonatal rat and mouse cardiac myocytes are mostly glycolytic (47,57) and mitochondria are randomly distributed throughout the cell (5,34).…”

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confidence: 99%

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Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment

Lyra-Leite

Andres

Petersen

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes. To test this, we developed a new procedure to transfer tunable polydimethylsiloxane disks microcontact-printed with fibronectin into cell culture microplates. We cultured Sprague-Dawley neonatal rat ventricular myocytes within the wells, which consistently formed tissues following the printed fibronectin, and measured oxygen consumption rate using a Seahorse extracellular flux analyzer. Our data indicate that parameters associated with baseline metabolism are predominantly regulated by ECM elasticity, whereas the ability of tissues to adapt to metabolic stress is regulated by both ECM elasticity and tissue alignment. Furthermore, bioenergetic health index, which reflects both the positive and negative aspects of oxygen consumption, was highest in aligned tissues on the most rigid substrate, suggesting that overall mitochondrial function is regulated by both ECM elasticity and tissue alignment. Our results demonstrate that mitochondrial function is regulated by both ECM elasticity and myofibril architecture in cardiac myocytes. This provides novel insight into how extracellular cues impact mitochondrial function in the context of cardiac development and disease. A new methodology has been developed to measure O consumption rates in engineered cardiac tissues with independent control over tissue alignment and matrix elasticity. This led to the findings that matrix elasticity regulates basal mitochondrial function, whereas both matrix elasticity and tissue alignment regulate mitochondrial stress responses.

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Section: Discussionmentioning

confidence: 87%

mentioning

confidence: 99%

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment

Lyra-Leite

Andres

Petersen

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

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“…Analysis of mtDNA/nDNA ratio. For a third measurement of mitochondrial content/density, mtDNA and nDNA were quantified and expressed as a ratio as previously described (62). Genomic DNA was isolated from 10-15 mg of the muscle biopsy specimen using a Nucleospin tissue kit (Takara).…”

Section: Methodsmentioning

confidence: 99%

Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants

Ryan¹,

Yamaguchi²,

Schmidt³

et al. 2018

JCI Insight

131

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“…In heart samples from 19 patients, p62, Beclin1, ATG5 and LC3-II degradation were recorded, suggesting an increased autophagic flux [171]. The same authors later asserted that mitophagy and mitochondrial biogenesis also take part in the HIR program by increasing their activation following cardiac surgery [73]. Despite the innovative approach and use of human samples in these studies, additional studies should further confirm this evidence because autophagy and mitophagy are complex and difficult to assess in tissues.…”

Section: Mitophagy In Human Cardiac Surgerymentioning

confidence: 95%

“…For example, the low levels of LC3-II detected in the first study [171] indicate both low autophagy induction and increased flux without protein replacement. In the second paper [73], mitophagy activation was inferred from Parkin translocation from the cytosol to mitochondria in heart samples before and after surgery and from decreased levels in optineurin (OPTN) and NDP52 receptors in the total homogenate; however, the translocation of these proteins into mitochondria and their clustering should be evaluated. Notably, a high percentage of patients being analyzed might be under statin treatment, which induces autophagy itself [172].…”

Section: Mitophagy In Human Cardiac Surgerymentioning

confidence: 99%

Mitophagy in Cardiovascular Diseases

Morciano

Patergnani

Bonora

et al. 2020

JCM

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Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.

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Mitophagy and mitochondrial biogenesis in atrial tissue of patients undergoing heart surgery with cardiopulmonary bypass

Cited by 57 publications

References 28 publications

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment

Mitochondrial function in engineered cardiac tissues is regulated by extracellular matrix elasticity and tissue alignment

Extensive skeletal muscle cell mitochondriopathy distinguishes critical limb ischemia patients from claudicants

Mitophagy in Cardiovascular Diseases

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