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Could Cytoplasmic Lipid Droplets be Linked to Inefficient Oxidative Phosphorylation in Cancer?

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Abstract

Purpose of Review

Triglyceride-rich cytoplasmic lipid droplets are present in many malignant cancers. It remains controversial as to whether the lipid droplets serve as reservoirs of respiratory fuel or are sequestered in droplets because they cannot be efficiently oxidized for energy. Cytoplasmic lipid droplets can arise from either hypoxia or from abnormalities in mitochondria structure and function. A hypothesis is presented suggesting that the lipid droplet accumulation is linked to inefficient oxidative phosphorylation.

Recent Findings

Evidence is reviewed showing that hypoxia-induced inhibition of oxidative phosphorylation can elicit the formation of cytoplasmic lipid droplets. Abnormalities in mitochondrial structure and function have been documented in malignant cancers where lipid droplets are also present.

Summary

The mitochondrial abnormalities seen in cancer cells would compromise the efficiency of oxidative phosphorylation and thus contribute to the accumulation of lipid droplets in the cytoplasm. The presence of cytoplasmic lipid droplets and the aerobic fermentation commonly seen in most malignant cancers can serve together as biomarkers for oxidative phosphorylation inefficiency.

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Acknowledgements

We thank the Foundation for Metabolic Cancer Therapies, CrossFit Inc., Broken Science Initiative, Dr. Joseph Maroon, Dr. Edward Miller, Kenneth Rainin Foundation, the Corkin Family Foundation, Children with Cancer UK, and the Boston College Research Expense Fund for their support.

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Authors and Affiliations

  1. Biology Department, Boston College, 140 Commonwealth Ave, Chestnut Hill, MA, 02467, USA

    Thomas N. Seyfried, Nathan L. Ta, Tomas Duraj & Derek C. Lee

  2. BPGbio, 500 Old Connecticut Path, Bldg B, Framingham, MA, 01701, USA

    Michael A. Kiebish

  3. Department of Medical Biochemistry, Semmelweis University, Budapest, 1094, Hungary

    Christos Chinopoulos

  4. Facultad de Medicina, Instituto de Investigaciones Biológicas, Universidad del Zulia, Postal Code: 526, Maracaibo, Venezuela

    Gabriel Arismendi-Morillo

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All authors read and approved the information presented in the manuscript. TNS wrote the manuscript. NLT, TD, DL, MK, CC, and GAM made material contributions to content.

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Michael A. Kiebish is VP of Platform and Translational Sciences for BPGbio with nothing else to disclose. All remaining authors declare they have no conflicts of interest.

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Seyfried, T.N., Ta, N.L., Duraj, T. et al. Could Cytoplasmic Lipid Droplets be Linked to Inefficient Oxidative Phosphorylation in Cancer?. Curr. Tissue Microenviron. Rep. (2024). https://doi.org/10.1007/s43152-024-00057-2

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