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

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.

Liraglutide Counteracts Endoplasmic Reticulum Stress in Palmitate-Treated Hypothalamic Neurons without Restoring Mitochondrial Homeostasis

“…Interestingly, metformin inhibits Drp1 activity in peripheral tissues [47]. On the other hand, inhibition of Drp1 blunts mitochondrial fission and fatty-acid oxidation in fibroblasts under conditions of palmitate exposure [67]. Consistent with the ability of metformin to inhibit mitochondrial fission, we find here that the drug protected against shrinkage of average mitochondrial area in neurons exposed to palmitate, while liraglutide does not.…”

“…In Sim1/MC4R neurons of the PVN, loss of MC4R is concomitant with fragmentation of mitochondrial network [7]. In vitro experiments have found that direct exposure to elevated palmitate induces fragmentation of mitochondria in insulinoma cells [46], podocytes [28], epithelial cells [67], and fibroblasts [68]. Similarly, we find here that direct exposure to elevated palmitate is sufficient to induce mitochondrial fragmentation and depolarization in hypothalamic neurons.…”

Protective Effects of Dexmedetomidine on Sepsis-Induced Vascular Leakage by Alleviating Ferroptosis via Regulating Metabolic Reprogramming

“…Many reports showed that mitochondrial morphology and mitochondrial metabolism interacted. For example, Song et al 43 inhibited mitochondrial fission by silencing Drp1 and found an increase in the fatty acid content of lipid droplets and a decrease in mitochondrial fatty acid oxidation, which clarified the role of mitochondrial dynamics in the control of intracellular fuel utilization and partitioning. The change of mitochondrial metabolism could model mitochondrial morphology.…”

Contribution of specific ceramides to obesity-associated metabolic diseases

“…It has been found that ceramides can modulate mitochondrial morphology through direct interaction with the fusion/fission machinery of mitochondrial membranes [ 26 ]. Transient morphological changes are necessary for a dynamic adaptation of mitochondrial (respiratory) function to a variety of metabolic cues, also to balance intracellular fuel utilization and partitioning [ 115 – 117 ]. It was initially observed that fatty acid turnover in cultured cells triggers mitochondrial fragmentation through increased de novo ceramide synthesis [ 118 ].…”