Intricate role of mitochondrial lipid in mitophagy and mitochondrial apoptosis: its implication in cancer therapeutics
Open accessAbstract
The efficacy of chemotherapy is mostly restricted by the drug resistance developed during the course of cancer treatment. Mitophagy, as a pro-survival mechanism, crucially maintains mitochondrial homeostasis and it is one of the mechanisms that cancer cells adopt for their progression. On the other hand, mitochondrial apoptosis, a precisely regulated form of cell death, acts as a tumor-suppressive mechanism by targeting cancer cells. Mitochondrial lipids, such as cardiolipin, ceramide, and sphingosine-1-phosphate, act as a mitophageal signal for the clearance of damaged mitochondria by interacting with mitophagic machinery as well as activate mitochondrial apoptosis via the release of cytochrome c into the cytoplasm. In the recent time, the lipid-mediated lethal mitophagy has also been used as an alternative approach to abolish the survival role of lipid in cancer. Therefore, by targeting mitochondrial lipids in cancer cells, the detailed mechanism linked to drug resistance can be unraveled. In this review, we precisely discuss the current knowledge about the multifaceted role of mitochondrial lipid in regulating mitophagy and mitochondrial apoptosis and its application in effective cancer therapy.
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Excessive lipid accumulation increases oxidative stress and promotes alterations in mitophagy.
“Excessive lipid accumulation has been reported to increase oxidative stress and promote alterations in mitophagy [40, 41].”
From Dyslipidemia-Induced Mitochondrial Dysfunctions in the Brains Does Not Reach Pathological Levels in the ApoE-Knockout Mice (2026) · cites this paper as [40]
The section “Ceramide: a critical regulator of mitophagy” (page unavailable) says that ceramide stress leads to ROS accumulation and, in glioblastoma cells, lethal mitophagy. It also describes ceramide accumulation under cellular stress. This supports the connection for a specific lipid and condition, but not the broader claim that excessive lipid accumulation generally increases oxidative stress and alters mitophagy. (LLM, conf=0.84)
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- Authors
- Praharaj, P. P., Naik, P. P., Panigrahi, D. P., Bhol, C. S., Mahapatra, K. K., Patra, S., Sethi, G., & Bhutia, S. K.
- Affiliations
- National Institute of Technology Rourkela (IN)
- National University of Singapore (SG)
- Corresponding author
- Bhutia, Sujit Kumar
- ORCID
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2018-12-11
- Volume
- 76
- Issue
- 9
- Pages
- 1641-1652
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11105358
- OpenAlex
- W2905213246
- Cited by
- 104
- References
- 8
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 17 · 2023: 13 · 2022: 17 · 2021: 12 · 2020: 18 · 2019: 12
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- DBT India Alliance (BT/PR7791/BRB/10/1187/2013)
- Board of Research in Nuclear Sciences (37(1)/14/38/2016-BRNS/37276)
- Science and Engineering Research Board (EMR/2016/001246)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- mitochondrial lipids, mitophagy, mitochondrial apoptosis, cardiolipin, ceramide, sphingosine-1-phosphate, cytochrome c release, mitochondrial homeostasis, chemoresistance, cancer therapeutics
- MeSH terms
- Cardiolipins, Ceramides, Humans, Lysophospholipids, Mitochondria, Neoplasms, Sphingosine, Apoptosis, Cytochromes c, Mitophagy
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