Manipulation of Mitochondria Dynamics Reveals Separate Roles for Form and Function in Mitochondria Distribution
Open accessAbstract
Mitochondria shape is controlled by membrane fusion and fission mediated by mitofusins, Opa1, and Drp1, whereas mitochondrial motility relies on microtubule motors. These processes govern mitochondria subcellular distribution, whose defects are emphasized in neurons because of their polarized structure. We have studied how perturbation of the fusion/fission balance affects mitochondria distribution in Drosophila axons. Knockdown of Marf or Opa1 resulted in progressive loss of distal mitochondria and in a distinct oxidative phosphorylation and membrane potential deficit. Downregulation of Drp1 rescued the lethality and bioenergetic defect caused by neuronal Marf RNAi, but induced only a modest restoration of axonal mitochondria distribution. Surprisingly, Drp1 knockdown rescued fragmentation and fully restored aberrant distribution of axonal mitochondria produced by Opa1 RNAi; however, Drp1 knockdown did not improve viability or mitochondria function. Our data show that proper morphology is critical for proper axonal mitochondria distribution independent of bioenergetic efficiency. The health of neurons largely depends on mitochondria function, but does not depend on shape or distribution.
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Similar changes in mitochondrial ultrastructure were observed in a recent study investigating acute downregulation of both Opa1 and Drp1 in Drosophila adult muscles.
“Similar changes were observed in a recent study that investigated the acute downregulation of both Opa1 and Drp1 in Drosophila adult muscles [33].”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [33]
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- Authors
- Trevisan, T., Pendin, D., Montagna, A., Bova, S., Ghelli, A. M., & Daga, A.
- Affiliations
- IRCCS Eugenio Medea (IT)
- University of Padua (IT)
- University of Bologna (IT)
- Corresponding author
- Daga, Andrea
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 23
- Issue
- 6
- Pages
- 1742-1753
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2799755002
- Cited by
- 86
- References
- 35
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 13 · 2021: 15 · 2020: 12 · 2019: 16 · 2018: 1
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by-nc-nd)
- Funders
- Italian Ministry of Health (Starting Grant 2015)
- Cariparo Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- mitochondrial dynamics, mitochondrial fusion, mitochondrial fission, mitochondrial motility, Marf, OPA1, Drp1, mitofusins, neuronal polarity, oxidative phosphorylation, mitochondrial membrane potential, Drosophila neurons, mitochondrial morphology
- MeSH terms
- Animals, Axons, Drosophila melanogaster, Larva, Mitochondria, Muscles, Neuromuscular Junction, Phenotype, Membrane Potential, Mitochondrial, Mitochondrial Dynamics
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