ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

Abstract

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation.

Incompatibility between mitochondrial and nuclear genomes during oogenesis results in ovarian failure and embryonic lethality

“…This embryonic lethality was a strict maternal effect dependent on the temperature of the mother, which rescue experiments suggest is caused by incompatibility between the nuclear Aatm V and mitochondrial tRNA tyr G:U alleles. The temperature-shift experiments suggested that early oogenesis is a temperature-sensitive period, which is known to be a crucial time for mitochondrial proliferation, transport and selection, and alleles of mitochondrial proteins can even influence early oocyte specification (Cox and Spradling, 2003;Hill et al, 2014;Hurd et al, 2016;Ma et al, 2014;Teixeira et al, 2015). Our analysis, however, did not reveal defects in mitochondrial number, transport or oocyte specification.…”

Exposure to the widely used herbicide atrazine results in deregulation of global tissue-specific RNA transcription in the third generation and is associated with a global decrease of histone trimethylation in mice

“…The dramatic reduction of Atpaf2 expression and deregulation of a large number of genes encoding ATP-binding proteins suggest that changes induced in embryonic germ cells are likely preserved in SG. Importantly, ATP synthase is a key protein required for germ cell differentiation (113) and expression changes in genes, encoding the subunits or assembly proteins of ATP synthase, such as Atpaf2 , could contribute to germ cell development. We also explored the idea that at least some changes in SG-derived lineages could originate in the cells that express POU5F1 as a key pluripotency factor.…”

Protein synthesis and degradation are essential to regulate germline stem cell homeostasis in Drosophila testes

“…These genes have never been identified in other stem cell-related RNAi screens. Interestingly, the loss of several subunits of mitochondrial ATP synthase leads to ovary differentiation defects (Teixeira et al, 2015). We did not identify any gene encoding mitochondrial ATP synthase subunits in our primary morphology screens.…”