Atpaf2, also known as F(1)-ATPase assembly factor 2, is a nuclear-encoded mitochondrial chaperone protein. It is an essential ancillary factor facilitating the biogenesis of mitochondrial ATP synthase, a key enzyme for mitochondrial energy provision [1,2,3]. Mutations in Atpaf2 are associated with isolated deficiency of ATP synthase, leading to severe metabolic diseases like early-onset mitochondrial encephalo-cardiomyopathies [1].

In functional studies, Atpaf2-KO mice were embryonically lethal, suggesting its crucial role in early development [3]. This indicates that Atpaf2 is indispensable for normal in vivo development processes, likely due to its role in ATP synthase biogenesis which is vital for energy-demanding cellular functions during embryogenesis.

In conclusion, Atpaf2 is essential for the biogenesis of mitochondrial ATP synthase, playing a crucial role in normal development as demonstrated by the embryonic lethality of Atpaf2-KO mice. Its malfunction is associated with severe mitochondrial diseases, highlighting the importance of understanding its function for the study and potential treatment of these disorders.

References:

1. Hejzlarová, K, Mráček, T, Vrbacký, M, Pecina, P, Houštěk, J. . Nuclear genetic defects of mitochondrial ATP synthase. In Physiological research, 63, S57-71. doi:. https://pubmed.ncbi.nlm.nih.gov/24564666/

2. Picková, Andrea, Paul, Jan, Petruzzella, Vittoria, Houstek, Josef. . Differential expression of ATPAF1 and ATPAF2 genes encoding F(1)-ATPase assembly proteins in mouse tissues. In FEBS letters, 551, 42-6. doi:. https://pubmed.ncbi.nlm.nih.gov/12965202/

3. Zhou, Zhou, Zhang, Kailiang, Liu, Zhiheng, Yang, Qinglin, Long, Qinqiang. 2021. ATPAF1 deficiency impairs ATP synthase assembly and mitochondrial respiration. In Mitochondrion, 60, 129-141. doi:10.1016/j.mito.2021.08.005. https://pubmed.ncbi.nlm.nih.gov/34375736/