bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2025–03–30
four papers selected by
Gavin McStay, Liverpool John Moores University



  1. FEBS Lett. 2025 Mar 24.
      Clioquinol has been thought of as the causative drug of subacute myelo-optic neuropathy (SMON). The underlying mechanisms of clioquinol toxicity, however, have not been elucidated in detail. Here, we revealed that clioquinol (20 μm) suppressed the expression of SCO1 and SCO2 copper chaperones for mitochondrial respiratory chain Complex IV (cytochrome c oxidase) in SH-SY5Y neuroblastoma cells. The assembly of Complex IV components and Complex IV activity were suppressed in clioquinol-treated cells. Clioquinol (10-50 μm) decreased cellular ATP levels in glucose-free media. Clioquinol (10-50 μm) induced OMA1 mitochondrial protease-dependent degradation of the dynamin-related GTPase OPA1 and suppressed the expression of CHCHD10 and CHCHD2 involved in the maintenance of cristae structure. These results suggest that mitochondrial toxicity is one of the mechanisms of clioquinol-induced neuronal cell death.
    Keywords:  CHCHD10; OMA1; SCO2; SMON; clioquinol; mitochondria
    DOI:  https://doi.org/10.1002/1873-3468.70033
  2. Trends Cell Biol. 2025 Mar 26. pii: S0962-8924(25)00042-X. [Epub ahead of print]
      While mitochondrial dysfunction is one of the canonical hallmarks of aging, it remains only vaguely defined. Its core feature embraces defects in energy-producing molecular machinery, the mitochondrial respiratory complexes (MRCs). The causes and consequences of these defects hold research attention. In this review, we assess the lifecycle of respiratory complexes, from biogenesis to degradation, and look closely at the mechanisms that could underpin their dysfunction in aged cells. We discuss how these processes could be altered by aging and expand on the fate of MRCs in age-associated pathologies. Given the complexity behind MRC maintenance and functionality, several traits could contribute to the phenomenon known as age-associated mitochondrial dysfunction. New advances will help us better understand the fate of this machinery in aging and age-related diseases.
    Keywords:  OXPHOS; age-associated diseases; dysfunction; mitochondria; protein complexes, aging hallmarks
    DOI:  https://doi.org/10.1016/j.tcb.2025.02.008
  3. Genes (Basel). 2025 Mar 17. pii: 347. [Epub ahead of print]16(3):
      Mitochondria are vital organelles responsible for ATP production and metabolic regulation, essential for energy-intensive cells such as retinal ganglion cells. Dysfunction in mitochondrial oxidative phosphorylation or mitochondrial DNA (mtDNA) pathogenic variants can disrupt ATP synthesis, cause oxidative stress, and lead to cell death. This has profound implications for tissues such as the retina, optic nerve, and retinal pigment epithelium, which are dependent on robust mitochondrial function. In this review, we provide a comprehensive compilation of pathogenic variants in the mtDNA associated with various ophthalmic diseases, including Leber's hereditary optic neuropathy, chronic progressive external ophthalmoplegia, Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, among others. We highlight the genetic variants implicated in these conditions, their pathogenic roles, and the phenotypic consequences of mitochondrial dysfunction in ocular tissues. In addition to well-established mutations, we also discuss the emerging evidence of the role of mtDNA's variants in complex multifactorial diseases, such as non-arteritic anterior ischemic optic neuropathy, primary open-angle glaucoma, and age-related macular degeneration. The review aims to serve as a valuable resource for clinicians and researchers, providing a detailed overview of mtDNA pathogenic variants and their clinical significance in the context of mitochondrial-related eye diseases.
    Keywords:  DNA pathogenic variant; mitochondria; ophthalmology
    DOI:  https://doi.org/10.3390/genes16030347