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

Antioxidants & redox signaling

PubMedID: 22746225

Willems P, Wanschers BF, Esseling J, Szklarczyk R, Kudla U, Duarte I, Forkink M, Nooteboom M, Swarts H, Gloerich J, Nijtmans L, Koopman W, Huynen MA. BOLA1 is an aerobic protein that prevents mitochondrial morphology changes induced by glutathione depletion. Antioxid Redox Signal. 2013;18(2):129-38.
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.