1. Academic Validation
  2. BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion

BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion

  • Antioxid Redox Signal. 2013 Jan 10;18(2):129-38. doi: 10.1089/ars.2011.4253.
Peter Willems 1 Bas F J Wanschers John Esseling Radek Szklarczyk Urszula Kudla Isabel Duarte Marleen Forkink Marco Nooteboom Herman Swarts Jolein Gloerich Leo Nijtmans Werner Koopman Martijn A Huynen
Affiliations

Affiliation

  • 1 Department of Biochemistry, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Abstract

Aims: The BolA protein family is widespread among eukaryotes and bacteria. In Escherichia coli, BolA causes a spherical cell shape and is overexpressed during oxidative stress. Here we aim to elucidate the possible role of its human homolog BOLA1 in mitochondrial morphology and thiol redox potential regulation.

Results: We show that BOLA1 is a mitochondrial protein that counterbalances the effect of L-buthionine-(S,R)-sulfoximine (BSO)-induced glutathione (GSH) depletion on the mitochondrial thiol redox potential. Furthermore, overexpression of BOLA1 nullifies the effect of BSO and S-nitrosocysteine on mitochondrial morphology. Conversely, knockdown of the BOLA1 gene increases the oxidation of mitochondrial thiol groups. Supporting a role of BOLA1 in controlling the mitochondrial thiol redox potential is that BOLA1 orthologs only occur in aerobic eukaryotes. A measured interaction of BOLA1 with the mitochondrial monothiol glutaredoxin GLRX5 provides hints for potential mechanisms behind BOLA1's effect on mitochondrial redox potential. Nevertheless, we have no direct evidence for a role of GLRX5 in BOLA1's function.

Innovation: We implicate a new protein, BOLA1, in the regulation of the mitochondrial thiol redox potential.

Conclusion: BOLA1 is an aerobic, mitochondrial protein that prevents mitochondrial morphology aberrations induced by GSH depletion and reduces the associated oxidative shift of the mitochondrial thiol redox potential.

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