Mitochondrial Autophagy

Abstract

Efficient and functional mitochondrial networks are essential for myocardial contraction and cardiomyocyte survival. Mitochondrial autophagy (mitophagy) refers to selective sequestration of mitochondria by autophagosomes, which subsequently deliver them to lysosomes for destruction. This process is essential for myocardial homeostasis and adaptation to stress. Elimination of damaged mitochondria protects against cell death, as well as stimulates mitochondrial biogenesis. Mitophagy is a tightly controlled and highly selective process. It is modulated by mitochondrial fission and fusion proteins, BCL-2 family proteins, and the PINK1/Parkin pathway. Recent studies have provided evidence that miRNAs can regulate mitophagy by controlling the expression of essential proteins involved in the process. Disruption of autophagy leads to rapid accumulation of dysfunctional mitochondria, and diseases associated with impaired autophagy produce severe cardiomyopathies. Thus, autophagy and mitophagy pathways hold promise as new therapeutic targets for clinical cardiac care.

Assessing Cardiac Metabolism

“…254,256 Mitophagy is particularly important because it removes the damaged mitochondria that might otherwise contribute to a progressive bioenergetic dysfunction and programmed cell death. 257 …”

Mitochondrial function as a therapeutic target in heart failure

“…Although they are symbiotic partners with the other cellular compartments, mitochondria are in many ways discrete entities. Mitochondrial dynamics in the form of fission, fusion, and autophagy are highly regulated processes that are essential for energy production and structural integrity of the organelles 22–29 . Altered mitochondrial biogenesis, fragmentation, and hyperplasia have been observed in studies of human 30 and animal models 31,32 of HF.…”

Mitochondrial dysfunction in cardiac aging

“…Upon loss of mitochondrial membrane potential, PINK1 accumulates on the mitochondrial outer membrane and recruits Parkin, an E3 ubiquitin ligase, leading to the poly-ubiquitination of many mitochondrial outer membrane proteins such as Hexokinase I, VCAC1, MFN1/2, and Miro [176]. These ubquitinated proteins are recognized by autophagy proteins P62, LC3 II, and BNIP3 to promote fusion with the lysome and clearance of the dysfunctional organelle via mitophagy [176, 177]. Many of the details surrounding this pathway and the interactions starting at PINK1 and leading up to mitophagy have been studied in detail and reviewed elsewhere [170, 172, 176, 177].…”

“…These ubquitinated proteins are recognized by autophagy proteins P62, LC3 II, and BNIP3 to promote fusion with the lysome and clearance of the dysfunctional organelle via mitophagy [176, 177]. Many of the details surrounding this pathway and the interactions starting at PINK1 and leading up to mitophagy have been studied in detail and reviewed elsewhere [170, 172, 176, 177]. …”