The i -AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission
Open accessAbstract
Mitochondrial fusion and structure depend on the dynamin-like GTPase OPA1, whose activity is regulated by proteolytic processing. Constitutive OPA1 cleavage by YME1L and OMA1 at two distinct sites leads to the accumulation of both long and short forms of OPA1 and maintains mitochondrial fusion. Stress-induced OPA1 processing by OMA1 converts OPA1 completely into short isoforms, inhibits fusion, and triggers mitochondrial fragmentation. Here, we have analyzed the function of different OPA1 forms in cells lacking YME1L, OMA1, or both. Unexpectedly, deletion of Oma1 restored mitochondrial tubulation, cristae morphogenesis, and apoptotic resistance in cells lacking YME1L. Long OPA1 forms were sufficient to mediate mitochondrial fusion in these cells. Expression of short OPA1 forms promoted mitochondrial fragmentation, which indicates that they are associated with fission. Consistently, GTPase-inactive, short OPA1 forms partially colocalize with ER–mitochondria contact sites and the mitochondrial fission machinery. Thus, OPA1 processing is dispensable for fusion but coordinates the dynamic behavior of mitochondria and is crucial for mitochondrial integrity and quality control.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Under stress conditions, fusion can rely only on OPA1L, while OPA1S forms are dispensable.
“However, under stress conditions, fusion can rely only on OPA1L, while OPA1S forms are dispensable [76].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [76]
Complete conversion of OPA1L into OPA1S inhibits fusion and increases mitochondrial fission.
“On the contrary, the complete conversion of OPA1L into OPA1S inhibits fusion and increases mitochondrial fission [74, 76].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [76]
YME1L1 cuts site S2 in exon 5b of OPA1L splicing variants 4, 6, 7, and 8 under high OXPHOS conditions.
“YME1L1 cuts the site S2 in exon 5b of a subset of OPA1L belonging to the splicing variants 4, 6, 7, and 8 [76] under high OXPHOS conditions [77].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [76]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 52 · Cited by 812
- Authors
- Anand, R., Wai, T., Baker, M. J., Kladt, N., Schauss, A. C., Rugarli, E., & Langer, T.
- Affiliations
- University of Cologne (DE)
- Corresponding author
- Langer, Thomas
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2014-03-10
- Volume
- 204
- Issue
- 6
- Pages
- 919-929
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC3998800
- OpenAlex
- W2025449918
- Cited by
- 812
- References
- 52
- Citations by year
- 2026: 59 · 2025: 58 · 2024: 82 · 2023: 80 · 2022: 71 · 2021: 94 · 2020: 79 · 2019: 75 · 2018: 59 · 2017: 58 · 2016: 50 · 2015: 30 · 2014: 15
- FWCI
- 20.92
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- HAL (submittedVersion)
- 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
- OPA1, YME1L, OMA1, mitochondrial fusion, mitochondrial fission, proteolytic processing, dynamin-like GTPase, mitochondrial fragmentation, mitochondrial tubulation, ER-mitochondria contact sites, apoptosis resistance, mitochondrial quality control
- MeSH terms
- Animals, Humans, Metalloendopeptidases, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Apoptosis, GTP Phosphohydrolases, Protein Subunits, Protein Transport, Mitochondrial Proteins, Metalloproteases, Mice, Organelle Shape, Mitochondrial Size, HEK293 Cells, Mitochondrial Dynamics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
