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Verma, Yash; Mehra, Upasana; Pandey, Dharmendra Kumar; Kar, Joy; Perez-Martinez, Xochitl; Jana, Siddhartha S; Datta, Kaustuv (2021)

MRX8, THE CONSERVED MITOCHONDRIAL YIHA GTPASE FAMILY MEMBER, IS REQUIRED FOR DE NOVO COX1 SYNTHESIS AT SUBOPTIMAL TEMPERATURES IN SACCHAROMYCES CEREVISIAE

Mol Biol Cell 32(21):
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The synthesis of Cox1, the conserved catalytic-core subunit of Complex IV, a multisubunit machinery of the mitochondrial oxidative phosphorylation (OXPHOS) system under environmental stress, has not been sufficiently addressed. In this study, we show that the putative YihA superfamily GTPase, Mrx8, is a bona fide mitochondrial protein required for Cox1 translation initiation and elongation during suboptimal growth condition at 16°C. Mrx8 was found in a complex with mitochondrial ribosomes, consistent with a role in protein synthesis. Cells expressing mutant Mrx8 predicted to be defective in guanine nucleotide binding and hydrolysis were compromised for robust cellular respiration. We show that the requirement of Pet309 and Mss51 for cellular respiration is not bypassed by overexpression of Mrx8 and vice versa. Consistently the ribosomal association of Mss51 is independent of Mrx8. Significantly, we find that , the human orthologue, complements the loss of cellular respiration in cells and GTPBP8 localizes to the mitochondria in mammalian cells. This strongly suggests a universal role of the family of proteins in regulating mitochondrial function.