bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2020‒04‒05
seven papers selected by
Gavin McStay
Staffordshire University

  1. Cell. 2020 Apr 02. pii: S0092-8674(20)30228-2. [Epub ahead of print]181(1): 168-188
    Russell OM, Gorman GS, Lightowlers RN, Turnbull DM.
      Mitochondrial diseases are clinically heterogeneous disorders caused by a wide spectrum of mutations in genes encoded by either the nuclear or the mitochondrial genome. Treatments for mitochondrial diseases are currently focused on symptomatic management rather than improving the biochemical defect caused by a particular mutation. This review focuses on the latest advances in the development of treatments for mitochondrial disease, both small molecules and gene therapies, as well as methods to prevent transmission of mitochondrial disease through the germline.
  2. Biol Chem. 2020 Mar 01. pii: /j/bchm.just-accepted/hsz-2020-0117/hsz-2020-0117.xml. [Epub ahead of print]
    Lill R.
      Protein cofactors often are the business ends of proteins, and are either synthesized inside cells or are taken up from the nutrition. A cofactor that strictly needs to be synthesized by cells is the iron-sulfur (Fe/S) cluster. This evolutionary ancient compound performs numerous biochemical functions including electron transfer, catalysis, sulfur mobilization, regulation, and protein stabilization. Since the discovery of eukaryotic Fe/S protein biogenesis two decades ago, more than 30 biogenesis factors have been identified in mitochondria and cytosol. They support the synthesis, trafficking and target-specific insertion of Fe/S clusters. In this review, I first summarize what led to the initial discovery of Fe/S protein biogenesis in yeast. I then discuss the function and localization of Fe/S proteins in (non-green) eukaryotes. The major part of the review provides a detailed synopsis of the three major steps of mitochondrial Fe/S protein biogenesis, i.e. the de novo synthesis of a [2Fe-2S] cluster on a scaffold protein, the Hsp70 chaperone-mediated transfer of the cluster and integration into [2Fe-2S] recipient apoproteins, and the reductive fusion of [2Fe-2S] to [4Fe-4S] clusters and their subsequent assembly into target apoproteins. Finally, I summarize the current knowledge of the mechanisms underlying the maturation of cytosolic and nuclear Fe/S proteins.
    Keywords:  ABC protein; CIA machinery; Fe/S cluster; Fe/S disease; ISC machinery; metallo proteins
  3. Biol Chem. 2020 Mar 01. pii: /j/bchm.just-accepted/hsz-2020-0121/hsz-2020-0121.xml. [Epub ahead of print]
    Tamura Y, Kawano S, Endo T.
      Mitochondria are surrounded by the two membranes, the outer and inner membranes, whose lipid compositions are optimized for proper functions and structural organizations of mitochondria. Although a part of mitochondrial lipids including their characteristic lipids, phosphatidylethanolamine and cardiolipin, are synthesized within mitochondria, their precursor lipids and other lipids are transported from other organelles, mainly the endoplasmic reticulum. Mitochondrially synthesized lipids are re-distributed within mitochondria and to other organelles, as well. Recent studies pointed to the important roles of inter-organelle contact sites in lipid trafficking between different organelle membranes. Identification of Ups/PRELI proteins as lipid transfer proteins shuttling between the mitochondrial outer and inner membranes established a part of the molecular and structural basis of the still elusive intra-mitochondrial lipid trafficking.
    Keywords:  ERMES; Ups/PRELI; cardiolipin; cristae; inter-organelle contact; mitochondria; phosphatidylethanolamine; phospholipids
  4. Microorganisms. 2020 Mar 31. pii: E494. [Epub ahead of print]8(4):
    Hewitt SK, Duangrattanalert K, Burgis T, Zeef LAH, Naseeb S, Delneri D.
      Mitochondrial DNA (mtDNA) in yeast is biparentally inherited, but colonies rapidly lose one type of parental mtDNA, thus becoming homoplasmic. Therefore, hybrids between the yeast species possess two homologous nuclear genomes, but only one type of mitochondrial DNA. We hypothesise that the choice of mtDNA retention is influenced by its contribution to hybrid fitness in different environments, and the allelic expression of the two nuclear sub-genomes is affected by the presence of different mtDNAs in hybrids. Saccharomyces cerevisiae/S. uvarum hybrids preferentially retained S. uvarum mtDNA when formed on rich media at colder temperatures, while S. cerevisiae mtDNA was primarily retained on non-fermentable carbon source, at any temperature. Transcriptome data for hybrids harbouring different mtDNA showed a strong environmentally dependent allele preference, which was more important in respiratory conditions. Co-expression analysis for specific biological functions revealed a clear pattern of concerted allelic transcription within the same allele type, which supports the notion that the hybrid cell works preferentially with one set of parental alleles (or the other) for different cellular functions. Given that the type of mtDNA retained in hybrids affects both nuclear expression and fitness, it might play a role in driving hybrid genome evolution in terms of gene retention and loss.
    Keywords:  hybrids yeast; mitochondria; nuclear transcription
  5. J Mol Biol. 2020 Mar 28. pii: S0022-2836(20)30259-X. [Epub ahead of print]
    Schlame M, Xu Y.
      Tafazzin is a mitochondrial enzyme that exchanges fatty acids between phospholipids by phospholipid-lysophospholipid transacylation. The reaction alters the molecular species composition and, as a result, the physical properties of lipids. In vivo, the most important substrate of tafazzin is the mitochondria-specific lipid cardiolipin. Tafazzin mutations cause the human disease Barth syndrome, which presents with cardiomyopathy, skeletal muscle weakness, fatigue, and other symptoms, probably all related to mitochondrial dysfunction. The reason why mitochondria require tafazzin is still not known but recent evidence suggests that tafazzin may lower the energy cost associated with protein crowding in the inner mitochondrial membrane.
    Keywords:  Barth syndrome; Cardiolipin; Membrane lipids; Mitochondria
  6. Nat Commun. 2020 Apr 02. 11(1): 1643
    Szczepanowska K, Senft K, Heidler J, Herholz M, Kukat A, Höhne MN, Hofsetz E, Becker C, Kaspar S, Giese H, Zwicker K, Guerrero-Castillo S, Baumann L, Kauppila J, Rumyantseva A, Müller S, Frese CK, Brandt U, Riemer J, Wittig I, Trifunovic A.
      Regulation of the turnover of complex I (CI), the largest mitochondrial respiratory chain complex, remains enigmatic despite huge advancement in understanding its structure and the assembly. Here, we report that the NADH-oxidizing N-module of CI is turned over at a higher rate and largely independently of the rest of the complex by mitochondrial matrix protease ClpXP, which selectively removes and degrades damaged subunits. The observed mechanism seems to be a safeguard against the accumulation of dysfunctional CI arising from the inactivation of the N-module subunits due to attrition caused by its constant activity under physiological conditions. This CI salvage pathway maintains highly functional CI through a favorable mechanism that demands much lower energetic cost than de novo synthesis and reassembly of the entire CI. Our results also identify ClpXP activity as an unforeseen target for therapeutic interventions in the large group of mitochondrial diseases characterized by the CI instability.
  7. J Neurol Sci. 2020 Mar 19. pii: S0022-510X(20)30127-1. [Epub ahead of print]412 116791
    Ueki K, Wakisaka Y, Nakamura K, Shono Y, Wada S, Yoshikawa Y, Matsukuma Y, Uchiumi T, Kang D, Kitazono T, Ago T.
    Keywords:  Digital PCR; Elderly onset; Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; Non-convulsive status epilepticus; m.3243A > G