Schwartz, A. Z. | bioRxiv Science

bioRxiv2023

Germline TFAM levels regulate mitochondrial DNA copy number and mutant heteroplasmy in C. elegans

The mitochondrial genome (mtDNA) is packaged into discrete protein-DNA complexes called nucleoids. mtDNA packaging factor TFAM (mitochondrial transcription factor-A) promotes nucleoid compaction and is required for mtDNA replication. Here, we investigate how changing TFAM levels affects mtDNA in the Caenorhabditis elegans germ line. We show that increasing germline TFAM activity boosts mtDNA number and significantly increases the relative proportion of a selfish mtDNA mutant, uaDf5. We conclude that TFAM levels must be tightly controlled to ensure appropriate mtDNA composition in the germ line.

cell biology↗

bioRxiv2022

Independent regulation of mtDNA quantity and quality resets the mitochondrial genome in C. elegans primordial germ cells

Mitochondria contain an independent genome, called mtDNA, which contains essential metabolic genes. Although mtDNA mutations occur at high frequency, they are inherited infrequently, indicating that germline mechanisms limit their accumulation. To determine how germline mtDNA is regulated, we examined the control of mtDNA quantity and quality in C. elegans primordial germ cells (PGCs). We show that PGCs generate a bottleneck in mtDNA number by segregating mitochondria into lobe-like protrusions that are cannibalized by adjacent cells, reducing mtDNA content two-fold. As PGCs exit quiescence and divide, mtDNAs replicate to maintain a set point of [~]200 mtDNAs per germline stem cell. Whereas PGC lobe cannibalism eliminates mtDNAs stochastically, we show that the kinase PINK1, operating independently of Parkin and autophagy, preferentially reduces the fraction of mutant mtDNAs. Thus, PGCs employ parallel mechanisms to control both the quantity and quality of the founding population of germline mtDNAs.

cell biology↗