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Cytochrome c oxidase subunit 5B, mitochondrial precursor (Cytochrome c oxidase polypeptide Vb)


Role of Mitochondrial Complex IV in Age-Dependent Obesity.

Aging is associated with progressive white adipose tissue (WAT) enlargement initiated early in life, but the molecular mechanisms involved remain unknown. Here we show that mitochondrial complex IV (CIV) activity and assembly are already repressed in white adipocytes of middle-aged mice and involve a HIF1A-dependent decline of essential CIV components such as COX5B. At the molecular level, HIF1A binds to the Cox5b proximal promoter and represses its expression. Silencing of Cox5b decreased fatty acid oxidation and promoted intracellular lipid accumulation. Moreover, local in vivo Cox5b silencing in WAT of young mice increased the size of adipocytes, whereas restoration of COX5B expression in aging mice counteracted adipocyte enlargement. An age-dependent reduction in COX5B gene expression was also found in human visceral adipose tissue. Collectively, our findings establish a pivotal role for CIV dysfunction in progressive white adipocyte enlargement during aging, which can be restored to alleviate age-dependent WAT expansion.

MeSH Terms

  • Adipocytes, White
  • Adipose Tissue, White
  • Aging
  • Animals
  • Cell Size
  • Electron Transport Complex IV
  • Epididymis
  • Gene Expression Regulation
  • Gene Silencing
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Male
  • Mice
  • Mitochondria
  • Obesity
  • Promoter Regions, Genetic
  • Protein Binding


  • COX5B
  • HIF-1
  • aging
  • human adipose tissue
  • mitochondrial complex IV
  • mitochondrial dysfunction
  • obesity
  • white adipocytes

Loss of COX5B inhibits proliferation and promotes senescence via mitochondrial dysfunction in breast cancer.

COX5B, a peripheral subunit of the cytochrome c oxidase complex, has previously been reported to maintain the stability of this complex. However, its functions and mechanisms involved in breast cancer progression remain unclear. Here, by performing SILAC assays in breast cancer cell models and detecting COX5B expression in tissues, we found that COX5B expression was elevated in breast cancer. Down-regulation of COX5B in breast cancer cell lines can suppress cell proliferation and induced cell senescence which was accompanied by elevating production of IL-8 and other cytokines. Interestingly, conditioned medium from COX5B knockdown cells could promote breast cancer cell migration. Mechanistic studies reveal that COX5B silence induces an increase in production of ROS, depolarization of MMP and a decrease in ATP. What's more, silence of COX5B leads to metabolic disorders, such as increased glucose uptake and decreased lactate secretion. Collectively, our study shows that loss of COX5B induces mitochondrial dysfunction and subsequently leads to cell growth suppression and cell senescence. Cytokines such as IL-8 secreted by senescent cells may in turn alter the microenvironment which could enhance cell migration. These findings may provide a novel paradigm for the treatment which combined anti-cancer drugs with particular cytokine inhibitors such as IL-8 blockers.

MeSH Terms

  • Animals
  • Blotting, Western
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cellular Senescence
  • Electron Transport Complex IV
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Mice
  • Mitochondria
  • RNA, Small Interfering
  • Reactive Oxygen Species
  • Real-Time Polymerase Chain Reaction
  • Transfection


  • COX5B
  • cytokine
  • mitochondrial dysfunction
  • proliferation
  • senescence