RT Journal Article
SR Electronic
T1 PINK1 and parkin shape the organism-wide distribution of a deleterious mitochondrial genome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 576165
DO 10.1101/576165
A1 Arnaud Ahier
A1 Nadia Cummins
A1 Chuan-Yang Dai
A1 Jürgen Götz
A1 Steven Zuryn
YR 2020
UL http://biorxiv.org/content/early/2020/06/12/576165.abstract
AB In multiple species, certain tissue types are prone to acquiring greater loads of mitochondrial genome (mtDNA) mutations relative to others, however the mechanisms that drive these heteroplasmy differences are unknown. We found that the conserved PTEN-induced putative kinase (PINK1/PINK-1) and the E3 ubiquitin-protein ligase parkin (PDR-1), which are required for mitochondrial autophagy (mitophagy), underlie stereotyped differences in heteroplasmy of a deleterious mitochondrial genome mutation (ΔmtDNA) between major somatic tissues types in Caenorhabditis elegans. We demonstrate that tissues prone to accumulating ΔmtDNA have lower mitophagy responses than those with low mutation levels, such as neurons. Moreover, we show that ΔmtDNA heteroplasmy increases when proteotoxic species that are associated with neurodegenerative disease and mitophagy inhibition are overexpressed in the nervous system. Together, these results suggest that PINK1 and parkin drive organism-wide patterns of heteroplasmy and provide evidence of a causal link between proteotoxicity, mitophagy, and mtDNA mutation levels in neurons.Competing Interest StatementThe authors have declared no competing interest.