Mitochondria are key regulators of cell fate during disease. They control cell survival via the production of ATP that fuels cellular processes and, conversely, cell death via the induction of apoptosis through release of pro-apoptotic factors such as cytochrome C. Therefore, it is essential to have stringent quality control mechanisms to ensure a healthy mitochondrial network. Quality control mechanisms are largely regulated by mitochondrial dynamics and mitophagy. The processes of mitochondrial fission (division) and fusion allow for damaged mitochondria to be segregated and facilitate the equilibration of mitochondrial components such as DNA, proteins, and metabolites. The process of mitophagy are responsible for the degradation and recycling of damaged mitochondria. These mitochondrial quality control mechanisms have been well studied in chronic and acute pathologies such as Parkinson's disease, Alzheimer's disease, stroke, and acute myocardial infarction, but less is known about how these two processes interact and contribute to specific pathophysiologic states. To date, evidence for the role of mitochondrial quality control in acute and chronic disease is divergent and suggests that mitochondrial quality control processes can serve both survival and death functions depending on the disease state. This review aims to provide a synopsis of the molecular mechanisms involved in mitochondrial quality control, to summarize our current understanding of the complex role that mitochondrial quality control plays in the progression of acute vs chronic diseases and, finally, to speculate on the possibility that targeted manipulation of mitochondrial quality control mechanisms may be exploited for the rationale design of novel therapeutic interventions.

The purpose of this study was to document changes in height (cm), body weight (kg), and body composition (%fat) of American football players from 1942 to 2011. Published articles were identified from databases and cross-referencing of bibliographies. Studies selected met the requirements of (1) having 2 of 3 dependent (height, body weight, and body composition) variables reported in the results; (2) containing a skill level of college or professional; (3) providing measured not self-reported data; and (4) published studies in English language journals. The data were categorized into groups based on skill level (college and professional). The player positions were grouped into 3 categories: mixed linemen (offensive and defensive linemen, tight ends, and linebackers), mixed offensive backs (quarterback and running backs), and mixed skilled positions (defensive backs and wide receivers). Linear regression was used to provide slope estimates and 95% confidence intervals (CIs). Unpaired t-tests were used to determine whether an individual regression slope was significantly different from zero. Statistical significance was set at p < 0.017. College level players in all position groups have significantly increased body weight over time (95% CI: mixed lineman 0.338-0.900 kg·y(-1); mixed offensive backs 0.089-0.298 kg·y(-1); mixed skilled 0.078-0.334 kg·y(-1)). The college level mixed linemen showed a significant increase over time for height (95% CI: 0.034-0.188 cm·y(-1)) and body composition (0.046-0.275% fat per year). Significant increases in body weight over time were found for professional level mixed lineman (95% CI: 0.098-0.756 kg·y(-1)) and mixed offensive backs (95% CI: 0.1800-0.545 kg·y(-1)). There were no other significant changes at the professional level. These data demonstrate that body weight of all college players and professional mixed lineman have significantly increased from 1942 to 2011.

The current standard of care for acute myocardial infarction or ‘heart attack’ is timely restoration of blood flow to the ischemic region of the heart. While reperfusion is essential for the salvage of ischemic myocardium, re-introduction of blood flow paradoxically kills (rather than rescues) a population of previously ischemic cardiomyocytes—a phenomenon referred to as ‘lethal myocardial ischemia-reperfusion (IR) injury’. There is long-standing and exhaustive evidence that mitochondria are at the nexus of lethal IR injury. However, during the past decade, the paradigm of mitochondria as mediators of IR-induced cardiomyocyte death has been expanded to include the highly orchestrated process of mitochondrial quality control. Our aims in this review are to: (1) briefly summarize the current understanding of the pathogenesis of IR injury, and (2) incorporating landmark data from a broad spectrum of models (including immortalized cells, primary cardiomyocytes and intact hearts), provide a critical discussion of the emerging concept that mitochondrial dynamics and mitophagy (the components of mitochondrial quality control) may contribute to the pathogenesis of cardiomyocyte death in the setting of ischemia-reperfusion.

Mitochondrial dynamics and mitophagy are constitutive and complex systems that ensure a healthy mitochondrial network through the segregation and subsequent degradation of damaged mitochondria. Disruption of these systems can lead to mitochondrial dysfunction and has been established as a central mechanism of ischemia/reperfusion (I/R) injury. Emerging evidence suggests that mitochondrial dynamics and mitophagy are integrated systems; however, the role of this relationship in the context of I/R injury remains unclear. To investigate this concept, we utilized primary cortical neurons isolated from the novel dual-reporter mitochondrial quality control knockin mice (C57BL/6-Gt(ROSA)26Sortm1(CAG-mCherry/GFP)Ganl/J) with conditional knockout (KO) of Drp1 to investigate changes in mitochondrial dynamics and mitophagic flux during in vitro I/R injury. Mitochondrial dynamics was quantitatively measured in an unbiased manner using a machine learning mitochondrial morphology classification system, which consisted of four different classifications: network, unbranched, swollen, and punctate. Evaluation of mitochondrial morphology and mitophagic flux in primary neurons exposed to oxygen-glucose deprivation (OGD) and reoxygenation (OGD/R) revealed extensive mitochondrial fragmentation and swelling, together with a significant upregulation in mitophagic flux. Furthermore, the primary morphology of mitochondria undergoing mitophagy was classified as punctate. Colocalization using immunofluorescence as well as western blot analysis revealed that the PINK1/Parkin pathway of mitophagy was activated following OGD/R. Conditional KO of Drp1 prevented mitochondrial fragmentation and swelling following OGD/R but did not alter mitophagic flux. These data provide novel evidence that Drp1 plays a causal role in the progression of I/R injury, but mitophagy does not require Drp1-mediated mitochondrial fission.