bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2023–02–12
two papers selected by
Gavin McStay, Liverpool John Moores University
  1. The Journey of Mitochondrial Protein Import and the Roadmap to Follow.
  2. How hot can mitochondria be? Incubation at temperatures above 43 °C induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria.
  1. Int J Mol Sci. 2023 Jan 27. pii: 2479. [Epub ahead of print]24(3):
    The Journey of Mitochondrial Protein Import and the Roadmap to Follow.
    Mary Oluwadamilola Haastrup, Kunwar Somesh Vikramdeo, Seema Singh, Ajay Pratap Singh, Santanu Dasgupta.
      Mitochondria are double membrane-bound organelles that play critical functions in cells including metabolism, energy production, regulation of intrinsic apoptosis, and maintenance of calcium homeostasis. Mitochondria are fascinatingly equipped with their own genome and machinery for transcribing and translating 13 essential proteins of the oxidative phosphorylation system (OXPHOS). The rest of the proteins (99%) that function in mitochondria in the various pathways described above are nuclear-transcribed and synthesized as precursors in the cytosol. These proteins are imported into the mitochondria by the unique mitochondrial protein import system that consists of seven machineries. Proper functioning of the mitochondrial protein import system is crucial for optimal mitochondrial deliverables, as well as mitochondrial and cellular homeostasis. Impaired mitochondrial protein import leads to proteotoxic stress in both mitochondria and cytosol, inducing mitochondrial unfolded protein response (UPRmt). Altered UPRmt is associated with the development of various disease conditions including neurodegenerative and cardiovascular diseases, as well as cancer. This review sheds light on the molecular mechanisms underlying the import of nuclear-encoded mitochondrial proteins, the consequences of defective mitochondrial protein import, and the pathological conditions that arise due to altered UPRmt.
    Keywords:  diseases; mitochondria; mitochondrial protein import machineries; mitochondrial unfolded protein response; proteins
    DOI:  https://doi.org/10.3390/ijms24032479
  2. Mitochondrion. 2023 Feb 08. pii: S1567-7249(23)00011-9. [Epub ahead of print]
    How hot can mitochondria be? Incubation at temperatures above 43 °C induces the degradation of respiratory complexes and supercomplexes in intact cells and isolated mitochondria.
    Raquel Moreno-Loshuertos, Joaquín Marco-Brualla, Patricia Meade, Ruth Soler-Agesta, José A Enriquez, Patricio Fernández-Silva.
      Mitochondrial function generates an important fraction of the heat that contributes to cellular and organismal temperature maintenance, but the actual values of this parameter reached in the organelles is a matter of debate. The studies addressing this issue have reported divergent results: from detecting in the organelles the same temperature as the cell average or the incubation temperature, to increasing differences of up to 10 degrees above the incubation value. Theoretical calculations based on physical laws exclude the possibility of relevant temperature gradients between mitochondria and their surroundings. These facts have given rise to a conundrum or paradox about hot mitochondria. We have examined by Blue-Native electrophoresis, both in intact cells and in isolated organelles, the stability of respiratory complexes and supercomplexes at different temperatures to obtain information about their tolerance to heat stress. We observe that, upon incubation at values above 43 °C and after relatively short periods, respiratory complexes, and especially complex I and its supercomplexes, are unstable even when the respiratory activity is inhibited. These results support the conclusion that high temperatures (> 43 °C) cause damage to mitochondrial structure and function and question the proposal that these organelles can physiologically work at close to 50 °C.
    Keywords:  hyperthermia; mitochondria; respiratory complex; stability; supercomplex; temperature
    DOI:  https://doi.org/10.1016/j.mito.2023.02.002
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