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Cited by 68Mitochondrial Function and PathologyAutophagy in Disease and TherapyCell death mechanisms and regulation

Mitochondrial protein import is regulated by p17/PERMIT to mediate lipid metabolism and cellular stress

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Oleinik, Natalia, Kim, Jisun, Roth, Braden M., Selvam, Shanmugam Panneer, Gooz, Monika, Johnson, Roger H., Lemasters, John J., Ogretmen, Besim·2019·Science Advances
DOI 10.1126/sciadv.aax1978PMC PMC6739097
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Abstract

mice, compared to controls, in various metabolically active tissues, including brain, muscle, and pancreas. Thus, these data have implications in diseases associated with accumulation of damaged mitochondria such as cancer and/or neurodegeneration.

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  • CerS1/C18-ceramide-dependent mitophagy in cancer cells and neurons is driven by p17/PERMIT-dependent transport of newly transcribed CerS1 to mitochondria.

    “CerS1/C18-ceramide-dependent mitophagy in cancer cells and neurons is driven by the p17/PERMIT-dependent transport of newly transcribed CerS1 to the mitochondria (29).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [29]

    The Introduction and Results report that p17/PERMIT transports newly translated CerS1 to mitochondria, where CerS1-dependent C18-ceramide generation mediates mitophagy; the Results also demonstrate this pathway in cancer cells. The source says newly translated, not newly transcribed, CerS1. It shows p17/PERMIT-dependent mitophagy in mouse brain tissue but does not establish the claim specifically in neurons. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • ATAD3 mediates ER-mitochondrial contacts, allowing the bidirectional trafficking of proteins between the ER and mitochondria.

    “ATAD3 mediates ER-mitochondrial contacts, allowing the bidirectional trafficking of proteins between the ER and mitochondria (29).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [29]

    The Introduction (page unavailable) describes p17/PERMIT carrying CerS1 from the ER surface to mitochondria through ER–mitochondria contact sites. It does not identify ATAD3 as the mediator or describe protein trafficking in both directions; the Discussion (page unavailable) likewise describes ER-to-mitochondria trafficking. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Parkin (PRKN) is one of the proteins with a catalytic cysteine involved in ceramide-dependent mitophagy.

    “One of the proteins with a catalytic cysteine involved in ceramide-dependent mitophagy is Parkin (PRKN) (29).”

    From Alzheimer's Disease–Associated Amyloid-β Precursor Protein Prevents Aging Stress–Induced Mitophagy and Fumarate Depletion to Improve Antitumor Immunity (2025) · cites this paper as [29]

    The Results section describes ceramide-dependent mitophagy involving p17/PERMIT, CerS1, Drp1, and LC3, but does not identify Parkin as a participant or describe a catalytic cysteine in Parkin. A reference title mentions Parkin in relation to mitophagy, but not ceramide-dependent mitophagy; searches for Parkin and catalytic cysteine found no passage supporting the attributed claim. No page numbers are available in our copy. (LLM, conf=0.72)

    Experimental — accuracy not yet measured

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Authors
Oleinik, N., Kim, J., Roth, B. M., Selvam, S. P., Gooz, M., Johnson, R. H., Lemasters, J. J., & Ogretmen, B.
Affiliations
  • Medical University of South Carolina (US)
  • Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2019-09-06
Volume
5
Issue
9
Pages
eaax1978-eaax1978
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.aax1978
PMC
PMC6739097
OpenAlex
W2972783613
Cited by
68
References
4
Citations by year
2026: 8 · 2025: 8 · 2024: 5 · 2023: 24 · 2022: 5 · 2021: 11 · 2020: 7
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (CA088932, CA173687, DE016572, CA203628, CA214461)
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 protein import, permits, lipid metabolism, cellular stress, mitochondrial dysfunction, cancer, neurodegeneration
MeSH terms
Animals, Ceramides, Endoplasmic Reticulum, Humans, Membrane Proteins, Mice, Inbred C57BL, Mitochondria, Stress, Physiological, Mice, Knockout, Protein Transport, Mitochondrial Proteins, Lipid Metabolism, Sphingosine N-Acyltransferase, Mitochondrial Membranes, Mice, Mitophagy, CRISPR-Cas Systems

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