Abrogating Mitochondrial Dynamics in Mouse Hearts Accelerates Mitochondrial Senescence
Open accessAbstract
Mitochondrial fusion and fission are critical to heart health; genetically interrupting either is rapidly lethal. To understand whether it is loss of, or the imbalance between, fusion and fission that underlies observed cardiac phenotypes, we engineered mice in which Mfn-mediated fusion and Drp1-mediated fission could be concomitantly abolished. Compared to fusion-defective Mfn1/Mfn2 cardiac knockout or fission-defective Drp1 cardiac knockout mice, Mfn1/Mfn2/Drp1 cardiac triple-knockout mice survived longer and manifested a unique pathological form of cardiac hypertrophy. Over time, however, combined abrogation of fission and fusion provoked massive progressive mitochondrial accumulation that severely distorted cardiomyocyte sarcomeric architecture. Mitochondrial biogenesis was not responsible for mitochondrial superabundance, whereas mitophagy was suppressed despite impaired mitochondrial proteostasis. Similar but milder defects were observed in aged hearts. Thus, cardiomyopathies linked to dynamic imbalance between fission and fusion are temporarily mitigated by forced mitochondrial adynamism at the cost of compromising mitochondrial quantity control and accelerating mitochondrial senescence.
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?
Specific deletion of MFN1, MFN2, and DRP1 leads to less severe cardiomyopathy and delays mortality with respect to unopposed fission or fusion.
“For instance, the specific deletion of MFN1, MFN2, and DRP1 leads to less severe cardiomyopathy and delays mortality with respect to unopposed fission or fusion [217].”
From The connection between the dynamic remodeling of the mitochondrial network and the regulation of muscle mass (2021) · cites this paper as [217]
Specific abrogation of mitochondrial dynamics in the heart leads to less severe cardiomyopathy and reverts mortality compared to unopposed fission or fusion heart-specific mouse models.
“Like skeletal muscle, the specific abrogation of mitochondrial dynamics in the heart leads to less severe cardiomyopathy and reverts mortality in respect to unopposed fission or fusion heart-specific mice models [35].”
From Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles (2019) · cites this paper as [35]
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 309
- Authors
- Song, M., Franco, A., Fleischer, J. A., Zhang, L., & Dorn, G. W.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Dorn, Gerald W.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2017-12
- Volume
- 26
- Issue
- 6
- Pages
- 872-883.e5
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC5718956
- OpenAlex
- W2767030556
- Cited by
- 309
- References
- 52
- Citations by year
- 2026: 15 · 2025: 36 · 2024: 38 · 2023: 33 · 2022: 48 · 2021: 36 · 2020: 39 · 2019: 29 · 2018: 33 · 2017: 1
- FWCI
- 11.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R35HL135736, R01HL128071)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- mitochondrial dynamics, mitochondrial fusion, mitochondrial fission, Drp1, cardiac hypertrophy, cardiomyopathy, mitophagy, mitochondrial proteostasis, mitochondrial accumulation, aging heart, triple knockout mice
- MeSH terms
- Animals, Cell Line, Disease Models, Animal, Fibroblasts, Cardiomegaly, Heart Ventricles, Mitochondria, Heart, Mice, Knockout, GTP Phosphohydrolases, Mitochondrial Proteins, Myocytes, Cardiac, Dynamins, Mice, Mitochondrial Dynamics, Mitophagy
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
