Nuclear factor erythroid 2-related factor 2 induction abrogates mitochondrial stress through parkin regulation.

Narukkottil Safreena, Jimna Mohamed Ameer, Indu C Nair, Sibi P Ittiyavirah, Jason Cannon, Goutam Chandra

Cell Biology Laboratory, Centre for Development and Aging Research, Inter University Centre for Biomedical Research & Super Speciality Hospital, Mahatma Gandhi University Campus at Thalappady, Rubber Board PO, Kottayam, 686009, Kerala, India; School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA.Cell Biology Laboratory, Centre for Development and Aging Research, Inter University Centre for Biomedical Research & Super Speciality Hospital, Mahatma Gandhi University Campus at Thalappady, Rubber Board PO, Kottayam, 686009, Kerala, India; School of Health Sciences, Purdue University, West Lafayette, IN, 47907, USA. · pubmed

Paper

Abstract

Mitochondrial stress (MS) is a hallmark of a number of aging-associated neurodegenerative diseases, including Parkinson's disease (PD). Chronic MS in PD disrupts neuronal proteostasis, causing dopaminergic neurodegeneration through inactivation of an E3 ubiquitin ligase, parkin, although the mechanism of its inactivation is not understood. Here, we elucidate a mechanistic framework linking progressive changes in mitochondrial mass with MS-induced alterations in parkin activity. We showed that acute and chronic MS differentially modulate parkin activity and regulate mitochondrial biogenesis by transcriptional control of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), through parkin substrate PARIS (parkin-interacting substrate). Acute exposure to the PD neurotoxin, 1-methyl-4-phenylpyridinium (MPP

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Research summary

The paper claims that mitochondrial stress differentially modulates parkin activity and regulates mitochondrial biogenesis through PGC1α. This research is relevant as it addresses the mechanisms underlying mitochondrial dysfunction, which is a significant contributor to aging and age-related neurodegenerative diseases.

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