Mt-Keima detects PINK1-PRKN mitophagy in vivo with greater sensitivity than mito-QC
Abstrak
ABSTRACT PINK1 and PRKN, which cause Parkinson disease when mutated, form a quality control mitophagy pathway that is well-characterized in cultured cells. The extent to which the PINK1-PRKN pathway contributes to mitophagy in vivo, however, is controversial. This is due in large part to conflicting results from studies using one of two mitophagy reporters: mt-Keima or mito-QC. Studies using mt-Keima have generally detected PINK1-PRKN mitophagy in vivo, whereas those using mito-QC generally have not. Here, we directly compared the performance of mito-QC and mt-Keima in cell culture and in mice subjected to a PINK1-PRKN activating stress. We found that mito-QC was less sensitive than mt-Keima for mitophagy, and that this difference was more pronounced for PINK1-PRKN mitophagy. These findings suggest that mito-QC’s poor sensitivity may account for conflicting reports of PINK1-PRKN mitophagy in vivo and caution against using mito-QC as a reporter for PINK1-PRKN mitophagy. Abbreviations: DFP: deferiprone; EE: exhaustive exercise; FBS: fetal bovine serum; OAQ: oligomycin, antimycin, and Q-VD-OPH; OMM: outer mitochondrial membrane; PBS: phosphate-buffered saline; PD: Parkinson disease; UPS: ubiquitin-proteasome system.
Topik & Kata Kunci
Penulis (8)
Yi-Ting Liu
Danielle A. Sliter
Mario K. Shammas
Xiaoping Huang
Chunxin Wang
Hannah Calvelli
D. Maric
Derek P. Narendra
Akses Cepat
- Tahun Terbit
- 2021
- Bahasa
- en
- Total Sitasi
- 56×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1080/15548627.2021.1896924
- Akses
- Open Access ✓