Rsp5 and Mdm30 reshape the mitochondrial network in response to age-induced vacuole stress
Year: 2019
Type: article
Abstract: Mitochondrial decline is a hallmark of aging, and cells are equipped with many systems to regulate mitochondrial structure and function in response to stress and metabolic alterations. Here, using budding yeast, we identify a proteolytic pathway that contributes to alterations in mitochondrial structure in aged cells through control of the mitochondrial fusion GTPase Fzo1. We show that mitochondrial fragmentation in old cells correlates with reduced abundance of Fzo1, which is triggered by functional alterations in the vacuole, a known early event in aging. Fzo1 degradation is mediated by a proteolytic cascade consisting of the E3 ubiquitin ligases SCF Mdm30 and Rsp5, and the Cdc48 cofactor Doa1. Fzo1 proteolysis is activated by metabolic stress that arises from vacuole impairment, and loss of Fzo1 degradation severely impairs mitochondrial structure and function. Together, these studies identify a new mechanism for stress-responsive regulation of mitochondrial structure that is activated during cellular aging.
Source: Molecular Biology of the Cell
Institutions: University of Utah, Calico Life Sciences
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funders: Glenn Foundation for Medical Research, United Mitochondrial Disease Foundation, Fondation pour la Recherche Médicale, National Institutes of Health, University of California, Davis, School of Medicine, National Institute on Aging, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
OpenAlex ID: W2946995130