Alterations of PINK1-PRKN signaling in mice during normal aging
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 <i>in vitro</i> upon acute and complete depolarization of mitochondria, the significance of PINK1-PRKN mitophagy <i>in vivo</i> 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 <i>in vivo</i>, setting the stage for further investigations of the PINK1-PRKN pathway during stress and in relevant disease conditions.
Authors
- Ian G. Ganley (ORCID: https://orcid.org/0000-0003-1481-9407)
- Shigeto Sato
- Dennis W. Dickson (ORCID: https://orcid.org/0000-0001-7189-7917)
- Nobutaka Hattori (ORCID: https://orcid.org/0000-0002-2034-2556)
- Nicholas W. Kurchaba
- Xu Hou (ORCID: https://orcid.org/0000-0003-3011-4378)
- Justin H. Nguyen (ORCID: https://orcid.org/0000-0002-5520-3273)
- Takahisa Kanekiyo (ORCID: https://orcid.org/0000-0001-6751-9374)
- Fabienne C. Fiesel (ORCID: https://orcid.org/0000-0002-1919-9676)
- Tingxiang Yan (ORCID: https://orcid.org/0000-0002-2068-859X)
- Kelly L. Stauch (ORCID: https://orcid.org/0000-0001-7444-4403)
- Jens O. Watzlawik (ORCID: https://orcid.org/0000-0003-0610-0267)
- Zahra Baninameh (ORCID: https://orcid.org/0000-0003-4478-994X)
- DeLisa Fairweather (ORCID: https://orcid.org/0000-0003-3093-1810)
- Matthew S. Goldberg (ORCID: https://orcid.org/0000-0002-5172-9841)
- Wolfdieter Springer (ORCID: https://orcid.org/0000-0002-1178-3149)
- Damian Nicolas Di Florio (ORCID: https://orcid.org/0000-0003-1619-5394)
- Sachiko Noda
- Kang Lu (ORCID: https://orcid.org/0000-0002-7268-0047)
- Tyrique Richardson
Institutions
- University of Dundee (GB)
- Jacksonville College (US)
- WinnMed (US)
- University of Alabama at Birmingham (US)
- Juntendo University (JP)
- MRC Protein Phosphorylation and Ubiquitylation Unit (GB)
- Mayo Clinic in Florida (US)
- University of Nebraska Medical Center (US)
Publication Details
- Journal
- Autophagy Reports
- Published
- 2024-12-07
- DOI
- https://doi.org/10.1080/27694127.2024.2434379
- Citations
- 9
- Primary Topic
- Autophagy in Disease and Therapy
- Type
- article
- Field-Weighted Citation Impact
- 3.48
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
- Congressionally Directed Medical Research Programs