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  • Parkin does not prevent accelerated cardiac aging in mitochondrial DNA mutator mice.

Parkin does not prevent accelerated cardiac aging in mitochondrial DNA mutator mice.

JCI insight (2019-04-17)
Benjamin P Woodall, Amabel M Orogo, Rita H Najor, Melissa Q Cortez, Eileen R Moreno, Hongxia Wang, Ajit S Divakaruni, Anne N Murphy, Åsa B Gustafsson
ABSTRACT

The E3 ubiquitin ligase Parkin plays an important role in regulating clearance of dysfunctional or unwanted mitochondria in tissues, including the heart. However, whether Parkin also functions to prevent cardiac aging by maintaining a healthy population of mitochondria is still unclear. Here, we have examined the role of Parkin in the context of mtDNA damage and myocardial aging using a mouse model carrying a proofreading defective mitochondrial DNA polymerase gamma (POLG). We observed both decreased Parkin protein levels and development of cardiac hypertrophy in POLG hearts with age; however, cardiac hypertrophy in POLG mice was neither rescued, nor worsened by cardiac specific overexpression or global deletion of Parkin, respectively. Unexpectedly, mitochondrial fitness did not substantially decline with age in POLG mice when compared to WT. We found that baseline mitophagy receptor-mediated mitochondrial turnover and biogenesis were enhanced in aged POLG hearts. We also observed the presence of megamitochondria in aged POLG hearts. Thus, these processes may limit the accumulation of dysfunctional mitochondria as well as the degree of cardiac functional impairment in the aging POLG heart. Overall, our results demonstrate that Parkin is dispensable for constitutive mitochondrial quality control in a mtDNA mutation model of cardiac aging.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Mitofusin-2 (N-Terminal) antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Paris/ZNF746 Antibody, clone N196/16, clone N196/16, from mouse
Sigma-Aldrich
Anti-α-Tubulin antibody, Mouse monoclonal, clone B-5-1-2, purified from hybridoma cell culture