PT  - JOURNAL ARTICLE
AU  - Arnaud Ahier
AU  - Chuan-Yang Dai
AU  - Steven Zuryn
TI  - PINK1-parkin-mediated mitophagy generates stereotyped somatic mosaicism of the mitochondrial genome
AID  - 10.1101/576165
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 576165
4099  - http://biorxiv.org/content/early/2019/03/12/576165.short
4100  - http://biorxiv.org/content/early/2019/03/12/576165.full
AB  - Mitochondria are critical for complex life and are characterized by the presence of their own genome (mtDNA). The mtDNA makeup within each cell is in a constant state of flux through processes of mutation, replication, and degradation, resulting in a mosaic mtDNA landscape that inevitably varies between cells, tissues, and organs within individuals. However, despite the stochastic nature of these processes, mosaic patterns of mtDNA mutations can become stereotyped across the tissues of individuals in both invertebrate and vertebrate species. The mechanisms that determine the non-random spatiotemporal distribution of mtDNA mutations are unknown. We find that PTEN induced putative kinase (PINK1) and the E3 ubiquitin-protein ligase parkin drive the formation of mtDNA heteroplasmy disparity between the major somatic tissue types of C. elegans, generating a stereotyped genetic mosaicism of the mitochondrial genomic landscape. PINK1 and parkin are conserved mediators of mitochondrial autophagy (mitophagy), but while PINK1/parkin preferentially direct the removal of mtDNA mutations in neurons, intestinal cells, and hypodermal cells, they act non-selectively in muscle cells to reduce mitochondrial network volume. These data suggest that different cell types use alternative strategies to cope with mtDNA mutations and implicate the nuclear genome encoded PINK1/parkin signalling axis in shaping stereotyped mitochondrial genomic mosaicism across individuals.