Eight human OPA1 isoforms, long and short: What are they for?

Valentina Del Dotto; Mario Fogazza; Valerio Carelli; Michela Rugolo; Claudia Zanna

doi:10.1016/j.bbabio.2018.01.005

Eight human OPA1 isoforms, long and short: What are they for?

Biochim Biophys Acta Bioenerg. 2018 Apr;1859(4):263-269. doi: 10.1016/j.bbabio.2018.01.005. Epub 2018 Jan 31.

Authors

Valentina Del Dotto¹, Mario Fogazza², Valerio Carelli³, Michela Rugolo⁴, Claudia Zanna⁵

Affiliations

¹ Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy.
² Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy.
³ Unit of Neurology, Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, Bologna, Italy; IRCCS Institute of Neurological Sciences of Bologna (ISNB), Bellaria Hospital, Bologna, Italy.
⁴ Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy. Electronic address: [email protected].
⁵ Department of Pharmacy and Biotechnology (FABIT), University of Bologna, Bologna, Italy. Electronic address: [email protected].

PMID: 29382469
DOI: 10.1016/j.bbabio.2018.01.005

Abstract

OPA1 is a dynamin-related GTPase that controls mitochondrial dynamics, cristae integrity, energetics and mtDNA maintenance. The exceptional complexity of this protein is determined by the presence, in humans, of eight different isoforms that, in turn, are proteolytically cleaved into combinations of membrane-anchored long forms and soluble short forms. Recent advances highlight how each OPA1 isoform is able to fulfill "essential" mitochondrial functions, whereas only some variants carry out "specialized" features. Long forms determine fusion, long or short forms alone build cristae, whereas long and short forms together tune mitochondrial morphology. These findings offer novel challenging therapeutic potential to gene therapy.

Keywords: Cristae; Energetics; Long and short OPA1 forms; Mitochondrial network dynamics; OPA1; mtDNA.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alternative Splicing*
Animals
DNA, Mitochondrial / chemistry
DNA, Mitochondrial / genetics
DNA, Mitochondrial / metabolism
GTP Phosphohydrolases / chemistry
GTP Phosphohydrolases / genetics*
GTP Phosphohydrolases / metabolism
GTP Phosphohydrolases / therapeutic use
Gene Expression
Genetic Therapy / methods
Humans
Isoenzymes / chemistry
Isoenzymes / genetics
Isoenzymes / metabolism
Isoenzymes / therapeutic use
Mitochondria / enzymology*
Mitochondria / ultrastructure
Mitochondrial Dynamics / genetics
Mitochondrial Membranes / enzymology*
Mitochondrial Membranes / ultrastructure
Optic Atrophy, Autosomal Dominant / enzymology
Optic Atrophy, Autosomal Dominant / genetics
Optic Atrophy, Autosomal Dominant / pathology
Optic Atrophy, Autosomal Dominant / therapy*
Oxidative Phosphorylation

Substances

DNA, Mitochondrial
Isoenzymes
GTP Phosphohydrolases
OPA1 protein, human