Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells
Jae-Eun Song,
Tiago C. Alves,
Bernardo Stutz,
Matija Šestan-Peša,
Nicole Kilian,
Sungho Jin,
Sabrina Diano,
Richard G. Kibbey,
Tamas L. Horvath
Affiliations
Jae-Eun Song
Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
Tiago C. Alves
Laboratory Medicine, Institute for Clinical Chemistry, Technische Universität Dresden, 01069 Dresden, Germany
Bernardo Stutz
Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
Matija Šestan-Peša
Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
Nicole Kilian
Centre for Infectious Diseases, Parasitology, Heidelberg University Hospital, 69120 Heidelberg, Germany
Sungho Jin
Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY 10032, USA
Sabrina Diano
Institute of Human Nutrition, Columbia University Irving Medical Center, New York, NY 10032, USA
Richard G. Kibbey
Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
Tamas L. Horvath
Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA
In the presence of high abundance of exogenous fatty acids, cells either store fatty acids in lipid droplets or oxidize them in mitochondria. In this study, we aimed to explore a novel and direct role of mitochondrial fission in lipid homeostasis in HeLa cells. We observed the association between mitochondrial morphology and lipid droplet accumulation in response to high exogenous fatty acids. We inhibited mitochondrial fission by silencing dynamin-related protein 1(DRP1) and observed the shift in fatty acid storage-usage balance. Inhibition of mitochondrial fission resulted in an increase in fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation. Next, we overexpressed carnitine palmitoyltransferase-1 (CPT1), a key mitochondrial protein in fatty acid oxidation, to further examine the relationship between mitochondrial fatty acid usage and mitochondrial morphology. Mitochondrial fission plays a role in distributing exogenous fatty acids. CPT1A controlled the respiratory rate of mitochondrial fatty acid oxidation but did not cause a shift in the distribution of fatty acids between mitochondria and lipid droplets. Our data reveals a novel function for mitochondrial fission in balancing exogenous fatty acids between usage and storage, assigning a role for mitochondrial dynamics in control of intracellular fuel utilization and partitioning.
