bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2022‒02‒13
five papers selected by
Gavin McStay
Staffordshire University

  1. STAR Protoc. 2022 Mar 18. 3(1): 101135
      The assembly of mitochondrial respiratory complexes into supercomplexes has significant implications for mitochondrial function. This protocol details mitochondrial isolation from mouse tissues and the use of blue native gel electrophoresis (BN-PAGE) to separate pre-identified mitochondrial supercomplexes into different gel bands. We then describe the excision of the individual bands, followed by in-gel protein digestion and peptide desalting for mass spectrometry (MS)-based proteomics. This protocol provides a time-efficient measurement of the abundance and distribution of proteins within known supercomplexes. For complete details on the use and execution of this profile, please refer to Gonzalez-Franquesa et al. (2021).
    Keywords:  Mass Spectrometry; Metabolism; Protein Biochemistry; Proteomics
  2. Mov Disord Clin Pract. 2022 Feb;9(2): 218-228
      Background: Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only.Objectives: To fully characterize, both phenotypically and genotypically, NDUFA12-related mitochondrial disease.
    Methods: We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature.
    Results: Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel.
    Conclusions: Our case series expands phenotype-genotype correlations in NDUFA12-associated mitochondrial disease, providing evidence of intra- and inter-familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh-like syndromes - particularly with dystonia - as well as isolated optic atrophy.
    Keywords:  Leigh syndrome; NDUFA12; dystonia; optic atrophy; phenotypic heterogeneity
  3. Clin Case Rep. 2022 Feb;10(2): e05361
      Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by metabolic stroke, seizures, cognitive decline, lactic acidosis, ragged-red fibers, headache, and vomiting, and in 80% of cases due to the mtDNA variant m.3243A>G. We report the case of a MELAS patient carrying a variant in subunit-5 of the respiratory chain (MT-ND5), rarely reported in MELAS. The patient is a 33-year-old male, who experienced a series of stroke-like episodes (StLEs) since age 23 years, which manifested clinically as seizures transient sensory disturbances, weakness, and visual or cognitive impairment. Over 9 years, these StLEs were misinterpreted as ischemic strokes, respectively, as cerebral vasculitis. He presented with mild, recurrent elevations of the creatine kinase. Initially, anti-seizure drugs and steroids appeared to be beneficial. Despite good recovery of each single StLE, the patient experienced a progressive decline of cognitive functions and activities of daily living. Cerebral imaging showed corresponding stroke-like lesions in changing locations. At age 32y, genetic work-up revealed the variant m.13513G>A in MT-ND5. The patient profited significantly from a cocktail with anti-oxidants/cofactors. This case shows that the variant m.13513G>A in MT-ND5 can manifest as MELAS that StLEs recover spontaneously and that the course of MELAS is slowly progressive.
    Keywords:  MELAS; mtDNA; respiratory chain; seizures; stroke‐like episode
  4. Front Microbiol. 2022 ;13 806575
      Analysis of genome variation provides insights into mechanisms in genome evolution. This is increasingly appreciated with the rapid growth of genomic data. Mitochondrial genomes (mitogenomes) are well known to vary substantially in many genomic aspects, such as genome size, sequence context, nucleotide base composition and substitution rate. Such substantial variation makes mitogenomes an excellent model system to study the mechanisms dictating mitogenome variation. Recent sequencing efforts have not only covered a rich number of yeast species but also generated genomes from abundant strains within the same species. The rich yeast genomic data have enabled detailed investigation from genome variation into molecular mechanisms in genome evolution. This mini-review highlights some recent progresses in yeast mitogenome studies.
    Keywords:  GC-content; gene conversion; mobile introns; mutation; recombination; repeat
  5. Semin Cancer Biol. 2022 Feb 02. pii: S1044-579X(22)00023-2. [Epub ahead of print]
      Oxidative phosphorylation (OXPHOS) takes place in mitochondria and is the process whereby cells use carbon fuels and oxygen to generate ATP. Formerly OXPHOS was thought to be reduced in tumours and that glycolysis was the critical pathway for generation of ATP but it is now clear that OXPHOS, at least in many tumour types, plays a critical role in delivering the bioenergetic and macromolecular anabolic requirements of cancer cells. There is now great interest in targeting the OXPHOS and the electron transport chain for cancer therapy and in this review article we describe current therapeutic approaches and challenges.
    Keywords:  OXPHOS; cancer drugs; cancer metabolism; complex I; electron transport chain