ArticleAutophagy2022
Ceramide-induced mitophagy impairs ß-oxidation-linked energy production in PINK1 deficiency.
Article in Autophagy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 12 citations in OpenAlex.
- Lipid Metabolism Reprogramming in the Aging Brain: Glial-Mediated Pathogenic Mechanisms and Translational Strategies in Neurodegeneration.International journal of molecular sciences · 2026Review
- Ceramide-Induced Metabolic Stress Depletes Fumarate and Drives Mitophagy to Mediate Tumor Suppression.Cancer research · 2025Article
- Emerging roles of the acid sphingomyelinase/ceramide pathway in metabolic and cardiovascular diseases: Mechanistic insights and therapeutic implications.World journal of cardiology · 2025Review
- Endoplasmic Reticulum Proteins Impact Penetrance in aInternational journal of molecular sciences · 2025Article
- Fasting the mitochondria to prevent neurodegeneration: the role of ceramides.Frontiers in neuroscience · 2025Review
- Opportunistic pathogeniScience · 2024Article
- Chinese botanical drugs targeting mitophagy to alleviate diabetic kidney disease, a comprehensive review.Frontiers in pharmacology · 2024Review
- Mitochondrial Complex I Disruption Causes Broad Reorchestration of Plant Lipidome Including Chloroplast Lipids.International journal of molecular sciences · 2022Article
- 'Fly-ing' from rare to common neurodegenerative disease mechanisms.Trends in genetics : TIG · 2022Review
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitophagy and energy production are two functionalities in which PINK1 plays a key role. Loss of PINK1 is one of the genetic causes of Parkinson disease (PD), suggesting both processes are important in PD pathogenesis. Nonetheless, it remains unclear whether these processes are connected or independent of one another. Sphingolipids, including ceramide, have recently emerged as an important new player in the development of PD, however, how alterations in ceramide levels are mechanistically linked to PD remained elusive. In a recently published study, we demonstrated that ceramide accumulates in mitochondria and initiates ceramide-induced mitophagy, thereby compensating for the lack of PINK1-dependent mitophagy upon PINK1 deficiency. However, ceramide accumulation negatively affects ß-oxidation, further aggravating the electron transport chain (ETC) defect caused by PINK1 deficiency and resulting in an additional requirement for mitophagy. Thus, we showed that ceramide serves as a link between the ETC and mitophagy upon PINK1 deficiency. Interruption of this vicious cycle via stimulation of ß-oxidation or reduction of ceramide levels can provide a novel therapeutic target in the treatment of PINK1-related PD.
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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.