Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells

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 mi...

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Published inMetabolites Vol. 11; no. 5; p. 322
Main Authors Song, Jae-Eun, Alves, Tiago C., Stutz, Bernardo, Šestan-Peša, Matija, Kilian, Nicole, Jin, Sungho, Diano, Sabrina, Kibbey, Richard G., Horvath, Tamas L.
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LanguageEnglish
Published Switzerland MDPI AG 18.05.2021
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Abstract 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.
AbstractList 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.
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.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.
Author Šestan-Peša, Matija
Kilian, Nicole
Jin, Sungho
Song, Jae-Eun
Alves, Tiago C.
Horvath, Tamas L.
Stutz, Bernardo
Kibbey, Richard G.
Diano, Sabrina
AuthorAffiliation 1 Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism, Department of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06511, USA; jaeeun.song@yale.edu (J.-E.S.); bernardo.stutz@yale.edu (B.S.); matija.sestan-pesa@yale.edu (M.Š.-P.)
2 Laboratory Medicine, Institute for Clinical Chemistry, Technische Universität Dresden, 01069 Dresden, Germany; tiago.alves@uniklinikum-dresden.de
7 Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06511, USA
6 Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06511, USA; Richard.kibbey@yale.edu
8 Department of Ob/Gyn & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06511, USA
3 Centre for Infectious Diseases, Parasitology, Heidelberg University Hospital, 69120 Heidelberg, Germany; nicole.kilian@med.uni-heidelberg.de
5 Department of Molecular Pharmacology and Therapeutics, Columbia University Irving Medical Center, New York, NY 1003
AuthorAffiliation_xml – name: 8 Department of Ob/Gyn & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06511, USA
– name: 3 Centre for Infectious Diseases, Parasitology, Heidelberg University Hospital, 69120 Heidelberg, Germany; nicole.kilian@med.uni-heidelberg.de
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34069800$$D View this record in MEDLINE/PubMed
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Keywords lipid homeostasis
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Snippet 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...
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SubjectTerms Bioenergetics
Carnitine palmitoyltransferase
Cell cycle
Cytology
Dynamin
fatty acid oxidation
Fatty acids
Glucose
Homeostasis
Kinases
lipid homeostasis
Lipids
Metabolism
Mitochondria
mitochondrial dynamics
Morphology
Oxidation
Palmitoyltransferase
Proteins
Respiration
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Title Mitochondrial Fission Governed by Drp1 Regulates Exogenous Fatty Acid Usage and Storage in Hela Cells
URI https://www.ncbi.nlm.nih.gov/pubmed/34069800
https://www.proquest.com/docview/2532194826
https://www.proquest.com/docview/2536467384
https://pubmed.ncbi.nlm.nih.gov/PMC8157282
https://doaj.org/article/79220711625c484daab929828974ea71
Volume 11
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