Cytochrome c oxidase of mammals contains a testes‐specific isoform of subunit VIb—the counterpart to testes‐specific cytochrome c?

Abstract

Sperm motility is highly dependent on aerobic energy metabolism, of which the apparent rate-limiting step of the mitochondrial respiratory chain is catalyzed by cytochrome c oxidase (COX). COX is the only electron transport chain complex to display isoforms, consistent with its suggested rate-limiting role. Isoforms were previously described for four of the 13 subunits. We now report the discovery that COX subunit VIb displays a testes-specific isoform in human, bull, rat, and mouse (COX VIb-2). Analysis of a variety of rat and mouse tissues, including ovaries, demonstrates exclusive expression of VIb-2 in testes, whereas VIb-1 transcripts are absent in rodent testes, even at early developmental stages. In contrast, both isoforms are transcribed in human testes. In situ hybridizations with human, rat, and mouse testes sections reveal VIb-2 transcripts in all testicular cell types. Within the seminiferous tubules, VIb-1 shows stronger signals in the periphery than in the lumen. Previously, cytochrome c was the only component of the mitochondrial respiratory chain known to express a testes-specific isoform in mammals. COX subunit VIb connects the two COX monomers into the physiological dimeric form, and is the only COX subunit that, like cytochrome c, is solely located in the inter-membrane space. Significant differences between the isoform sequences, in particular changes in charged amino acids, suggest interactions with cytochrome c and sperm-specific energy requirements.

Nuclear Respiratory Factor 1 Regulates All Ten Nuclear-encoded Subunits of Cytochrome c Oxidase in Neurons

“…The transmembranous subunit VIII is located in close vicinity to subunit IV and has tissue-specific isoforms that are differentially expressed in different species. In cows, dogs, and rats, the heart isoform (VIIIH) differs from the liver isoform (VIIIL), whereas in human, sheep, and rabbit, one and the same isoform is expressed in all tissues examined (32,34,41). COX VIII-3 is mitochondrially targeted, and its sequence conservation implies a functional role in the COX holoenzyme with possible tissue specificity (34).…”

Mammalian sperm metabolism: oxygen and sugar, friend and foe

“…The genetic response to the milieu of this space has been expression of a sperm-specific isoform of cytochrome c, designated cytochrome c t to differentiate it from the somatic form, cytochrome c s (Goldberg et al, 1977;Hake and Hecht, 1993). The subunit VIb of cytochrome oxidase is the one subunit of this multiunit enzyme that accesses the intermembrane space; it too has a sperm-specific isoform (Hüttermann et al, 2003). The implication of these findings is that the sperm-specific subunit VIb provides the interaction site with cytochrome c t in the midpiece mitochondrial intermembrane space, but experimental support for this implication is thin.…”

Tumor Necrosis Factor α Inhibits Oxidative Phosphorylation through Tyrosine Phosphorylation at Subunit I of Cytochrome c Oxidase

“…There are three liver and heart type isoform pairs of subunits VIa, VIIa, and VIII (reviewed in Ref. 14) in addition to a lung-specific isoform of CcO subunit IV, a testes-specific isoform of subunit VIb, and a third isoform of subunit VIII (15)(16)(17); CcO is allosterically regulated through adenine nucleotides and thyroid hormone T2 (reviewed in Ref. 18); and there is clear evidence that CcO can be phosphorylated (19 -22).…”