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Curr Genet. 2019 Feb 19. doi: 10.1007/s00294-019-00942-6. [Epub ahead of print]

Mdivi-1 and mitochondrial fission: recent insights from fungal pathogens.

Author information

1
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia.
2
Protein, Science and Engineering, Callaghan Innovation, Christchurch, 8140, New Zealand.
3
Infection and Immunity Program and the Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, 3800, Australia. ana.traven@monash.edu.

Abstract

Mitochondrial fission shows potential as a therapeutic target in non-infectious human diseases. The compound mdivi-1 was identified as a mitochondrial fission inhibitor that acts against the evolutionarily conserved mitochondrial fission GTPase Dnm1/Drp1, and shows promising data in pre-clinical models of human pathologies. Two recent studies, however, found no evidence that mdivi-1 acts as a mitochondrial fission inhibitor and proposed other mechanisms. In mammalian cells, Bordt et al. showed that mdivi-1 inhibits complex I in mitochondria (Dev Cell 40:583, 2017). In a second study, we have recently demonstrated that mdivi-1 does not trigger a mitochondrial morphology change in the human yeast pathogen Candida albicans, but impacts on endogenous nitric oxide (NO) levels and inhibits the key virulence property of hyphal formation (Koch et al., Cell Rep 25:2244, 2018). Here we discuss recent insights into mdivi-1's action in pathogenic fungi and the potential and challenges for repurposing it as an anti-infective. We also outline recent findings on the roles of mitochondrial fission in human and plant fungal pathogens, with the goal of starting the conversation on whether the research field of fungal pathogenesis can benefit from efforts in other disease areas aimed at developing therapeutic inhibitors of mitochondrial division.

KEYWORDS:

Aspergillus fumigatus; Candida albicans; Cryptococcus neoformans; Fungal pathogens; Mdivi-1; Mitochondria; Mitochondrial fission

PMID:
30783741
DOI:
10.1007/s00294-019-00942-6

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