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Porplycia 2017 Am J Physiol Regul Integr Comp Physiol

From Bioblast
Publications in the MiPMap
Porplycia D, Lau GY, McDonald J, Chen Z, Richards JG, Moyes CD (2017) Subfunctionalization of COX4 paralogs in fish. Am J Physiol Regul Integr Comp Physiol 312:R671-R680.

Β» PMID: 28148493 Open Access

Porplycia D, Lau GY, McDonald J, Chen Z, Richards JG, Moyes CD (2017) Am J Physiol Regul Integr Comp Physiol

Abstract: Cytochrome c oxidase (COX) subunit 4 has two paralogs in most vertebrates. The mammalian COX4-2 gene is hypoxia responsive, and the protein has a disrupted ATP-binding site that confers kinetic properties on COX that distinguish it from COX4-1. The structure-function of COX4-2 orthologs in other vertebrates remains uncertain. Phylogenetic analyses suggest the two paralogs arose in basal vertebrates, but COX4-2 orthologs diverged faster than COX4-1 orthologs. COX4-1/4-2 protein levels in tilapia tracked mRNA levels across tissues, and did not change in hypoxia, arguing against a role for differential post-translational regulation of paralogs. The heart, and to a lesser extent the brain, showed a size-dependent shift from COX4-1 to COX4-2 (transcript and protein). ATP allosterically inhibited both velocity and affinity for oxygen in COX assayed from both muscle (predominantly COX4-2) and gill (predominantly COX4-1). We saw some evidence of cellular and subcellular discrimination of COX4 paralogs in heart. In cardiac ventricle, some non-cardiomyocyte cells were COX positive but lacked detectible COX4-2. Within heart, the two proteins partitioned to different mitochondrial subpopulations. Cardiac subsarcolemmal mitochondria had mostly COX4-1 and intermyofibrillar mitochondria had mostly COX4-2. Collectively, these data argue that, despite common evolutionary origins, COX4-2 orthologs of fish show unique patterns of subfunctionalization with respect to transcriptional and posttranslation regulation relative to the rodents and primates that have been studied to date. β€’ Keywords: Energy metabolism, Evolutionary physiology, Mitochondria, Whole genome duplication β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: CA Vancouver Richards JG


Labels: MiParea: Respiration, nDNA;cell genetics 


Organism: Fishes  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 

Regulation: ATP, Oxygen kinetics  Coupling state: LEAK  Pathway: CIV, ROX  HRR: Oxygraph-2k 

Labels, 2018-10