Novel role of COX6c in the regulation of oxidative phosphorylation and diseases

Abstract

Cytochrome c oxidase subunit VIc (COX6c) is one of the most important subunits of the terminal enzyme of the respiratory chain in mitochondria. Numerous studies have demonstrated that COX6c plays a critical role in the regulation of oxidative phosphorylation (OXPHOS) and energy production. The release of COX6c from the mitochondria may be a hallmark of the intrinsic apoptosis pathway. Moreover, The changes in COX6c expression are widespread in a variety of diseases and can be chosen as a potential biomarker for diagnosis and treatment. In light of its exclusive effects, we present the elaborate roles that COX6c plays in various diseases. In this review, we first introduced basic knowledge regarding COX6c and its functions in the OXPHOS and apoptosis pathways. Subsequently, we described the regulation of COX6c expression and activity in both positive and negative ways. Furthermore, we summarized the elaborate roles that COX6c plays in various diseases, including cardiovascular disease, kidney disease, brain injury, skeletal muscle injury, and tumors. This review highlights recent advances and provides a comprehensive summary of COX6c in the regulation of OXPHOS in multiple diseases and may be helpful for drug design and the prediction, diagnosis, treatment, and prognosis of diseases.

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease

“…Interestingly, some of the TCA cycle markers that were down-regulated in different AD brain areas, such as Mdh2, Sdhb, Sucla2, and Dld, were significantly up-regulated in the brain of our PS19 transgenic mice receiving fasudil treatment. Cox6c plays important role in oxidative phosphorylation and energy production and a decrease of its expression and activity has been observed in the brain of AD patients and associated with impaired metabolic activity and neuronal loss (Wang et al, 2022 ). Similarly, we also observed a decrease expression of Cox6c in PS19 mice, that was reverted to control animals by the treatment with fasudil.…”

SPRI: Spatial Pattern Recognition using Information based method for spatial gene expression data

“…Hsp90 family chaperones, particularly Hsp90ab1 , is closely associated with astrocytes, suggesting it’s possible association with Alzheimer’s disease mediated by the accumulation of intracellular hyperphosphorylated tau proteins and extracellular amyloid β peptide [28]. The decreased expression and activity of Cox6c in the temporal and parietal cortex of patients with Alzheimer’s disease suggests that it may be a potential biomarker for the diagnosis of brain diseases [29]. In addition, functional enrichment analyses were performed.…”

l-Cysteine-Triggered Regulation of the Mitochondrial Energy Metabolism To Enhance Chemotherapy of Triple-Negative Breast Cancer

“…15 OxPhos is a process of ATP production driven by electron transport in the mitochondrial respiratory chain. 16,17 Uncouplers are compounds that promote oxidation while inhibiting phosphorylation, which can capure the protons from electron transport chain, thus blocking ATP production. 18 nutrients, which are converted to heat but not ATP.…”

“…Different from most other tumor cells, TNBC cells obtain their energy mainly from oxidative phosphorylation (OxPhos) and not glycolysis . OxPhos is a process of ATP production driven by electron transport in the mitochondrial respiratory chain. , Uncouplers are compounds that promote oxidation while inhibiting phosphorylation, which can capure the protons from electron transport chain, thus blocking ATP production . Therefore, cells consume large quantities of nutrients, which are converted to heat but not ATP .…”