Alterations of PINK1-PRKN signaling in mice during normal aging
Year: 2024
Type: article
Abstract: ABSTRACT The ubiquitin kinase-ligase pair PINK1-PRKN identifies and selectively marks damaged mitochondria for elimination via the autophagy-lysosome system (mitophagy). While this cytoprotective pathway has been extensively studied in vitro upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy in vivo is less well established. Here we used a novel approach to study PINK1-PRKN signaling in different energetically demanding tissues of mice during normal aging. We demonstrate a generally increased expression of both genes and enhanced enzymatic activity with aging across tissue types. Collectively our data suggest a distinct regulation of PINK1-PRKN signaling under basal conditions with the most pronounced activation and flux of the pathway in mouse heart compared to brain or skeletal muscle. Our biochemical analyses complement existing mitophagy reporter readouts and provide an important baseline assessment in vivo, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.
Source: Autophagy Reports
Authors: Zahra Baninameh, Jens O. Watzlawik, Xu Hou, Tyrique Richardson, Nicholas W. Kurchaba, Tingxiang Yan, Damian N. Di Florio, DeLisa Fairweather, Lu Kang, Justin H. Nguyen, Takahisa Kanekiyo, Dennis W. Dickson, Sachiko Noda, Shigeto Sato, Nobutaka Hattori, Matthew S. Goldberg, Ian G. Ganley, Kelly L. Stauch, Fabienne C. Fiesel, Wolfdieter Springer
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
Funders: U.S. Department of Defense, Michael J. Fox Foundation for Parkinson's Research, Alzheimer's Association, American Parkinson Disease Association, Florida Department of Health, Ted Nash Long Life Foundation, National Institutes of Health, Medical Research Council, National Institute on Aging, National Heart, Lung, and Blood Institute, National Institute of Neurological Disorders and Stroke, Congressionally Directed Medical Research Programs
Awards: G1269895679, G1291621007, G2040153736, Mitochondrial Sirtuin 3 in Parkinson's disease, G3784939612, G4119534169, Role of viral mitophagosomes in driving sex differences in myocarditis, G4260266352, APOE4-linked mitophagy changes in human disease brain and iPSC models, G5850682332, Molecular mechanisms of PINK1-PRKN directed mitochondrial quality control, G6071768264, EARLY-ONSET PARKINSON'S DISEASE IS A MITOCHONDRIAL DISEASE: A NIGRAL MITOCHONDRIAL CYTOPATHY, Synergistic Interaction of amyloid-beta and alpha-synuclein in Lewy body Dementia, Mitophagy Signalling in Health and Disease, G7447593385, Early-Onset Parkinson's Disease Is a Mitochondrial Disease: A Nigral Mitochondrial Cytopathy, Selective autophagy in Alzheimer's disease and related dementias, Sex differences in exercise-induced mitochondrial function during viral myocarditis, G8926451774, G9000141408, G9000182597, G9000183948, G9000322407, Role of mitochondrial extracellular vesicles in CVB3 myocarditis by sex
OpenAlex ID: W4405137763