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bioRxiv · 10.1101/2022.05.06.490954

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

Schwartz, A. Z.·Tsyba, N.·Abdu, Y.·Patel, M. R.·Nance, J.
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Abstract

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.

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Schwartz, A. Z., Tsyba, N., Abdu, Y., Patel, M. R., Nance, J.. 2022-05-07. Independent regulation of mtDNA quantity and quality resets the mitochondrial genome in C. elegans primordial germ cells. https://doi.org/10.1101/2022.05.06.490954

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