ArticleNature metabolism2020
PKC downregulation upon rapamycin treatment attenuates mitochondrial disease.
Article in Nature metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- Leigh Syndrome Pathomechanism Involves Region-Specific Innate Immune Activation in Ndufs4 Knockout Mice.Cellular and molecular neurobiology · 2026Article
- Rictor/mTORC2 signaling pathway mediates Benzo[a]pyrene-induced renal injury.Scientific reports · 2025Article
- Ndufs4GeroScience · 2025Review
- Mitochondrial dysfunction enhances influenza pathogenesis by up-regulating de novo sialic acid biosynthesis.Science advances · 2025Article
- Leigh Syndrome: A Comprehensive Review of the Disease and Present and Future Treatments.Biomedicines · 2025Review
- Cannabidiol ameliorates mitochondrial disease via PPARγ activation in preclinical models.Nature communications · 2024Article
- Acarbose suppresses symptoms of mitochondrial disease in a mouse model of Leigh syndrome.Nature metabolism · 2023Article
- Targeting the biology of aging with mTOR inhibitors.Nature aging · 2023Review
- Article
- Cardiac Involvement in Mitochondrial Disorders.Current heart failure reports · 2023Review
- The immune system as a driver of mitochondrial disease pathogenesis: a review of evidence.Orphanet journal of rare diseases · 2022Review
- Metabolic rescue ameliorates mitochondrial encephalo-cardiomyopathy in murine and human iPSC models of Leigh syndrome.Clinical and translational medicine · 2022Article
- Ndufs4 knockout mouse models of Leigh syndrome: pathophysiology and intervention.Brain : a journal of neurology · 2022Review
- Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome.JCI insight · 2022Article
- On the dynamic and even reversible nature of Leigh syndrome: Lessons from human imaging and mouse models.Current opinion in neurobiology · 2022Review
- Article
- Mitochondrial augmentation of CD34NPJ Regenerative medicine · 2021Article
- An energetics perspective on geroscience: mitochondrial protonmotive force and aging.GeroScience · 2021Article
- mTORC2: The other mTOR in autophagy regulation.Aging cell · 2021Review
- Accessory Subunits of the Matrix Arm of Mitochondrial Complex I with a Focus on Subunit NDUFS4 and Its Role in Complex I Function and Assembly.Life (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
Leigh syndrome is a fatal neurometabolic disorder caused by defects in mitochondrial function. Mechanistic target of rapamycin (mTOR) inhibition with rapamycin attenuates disease progression in a mouse model of Leigh syndrome (Ndufs4 knock-out (KO) mouse); however, the mechanism of rescue is unknown. Here we identify protein kinase C (PKC) downregulation as a key event mediating the beneficial effects of rapamycin treatment of Ndufs4 KO mice. Assessing the impact of rapamycin on the brain proteome and phosphoproteome of Ndufs4 KO mice, we find that rapamycin restores mitochondrial protein levels, inhibits signalling through both mTOR complexes and reduces the abundance and activity of multiple PKC isoforms. Administration of PKC inhibitors increases survival, delays neurological deficits, prevents hair loss and decreases inflammation in Ndufs4 KO mice. Thus, PKC may be a viable therapeutic target for treating severe mitochondrial disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.