CPT1C promotes human mesenchymal stem cells survival under glucose deprivation through the modulation of autophagy

Human mesenchymal stem cells (hMSCs) are widely used in regenerative medicine. In some applications, they must survive under low nutrient conditions engendered by avascularity. Strategies to improve hMSCs survival may be of high relevance in tissue engineering. Carnitine palmitoyltransferase 1 C (CPT1C) is a pseudoenzyme exclusively expressed in neurons and cancer cells. In the present study, we show that CPT1C is also expressed in hMSCs and protects them against glucose starvation, glycolysis inhibition, and oxygen/glucose deprivation. CPT1C overexpression in hMSCs did not increase fatty acid oxidation capacity, indicating that the role of CPT1C in these cells is different from that described in tumor cells. The increased survival of CPT1C-overexpressing hMSCs observed during glucose deficiency was found to be the result of autophagy enhancement, leading to a greater number of lipid droplets and increased intracellular ATP levels. In fact, inhibition of autophagy or lipolysis was observed to completely block the protective effects of CPT1C. Our results indicate that CPT1C-mediated autophagy enhancement in glucose deprivation conditions allows a greater availability of lipids to be used as fuel substrate for ATP generation, revealing a new role of CPT1C in stem cell adaptation to low nutrient environments.

• Publication year

  2018

• Venue

  Scientific Reports

• Publication date

  2018-05-03

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/s41598-018-25485-7PMID 29725060PMCID 5934389
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• AMPA-receptor specific biogenesis complexes control synaptic transmission and intellectual ability

  2017cited by this paper
• Mesenchymal Stromal Cells Differentiating to Adipocytes Accumulate Autophagic Vesicles Instead of Functional Lipid Droplets

  2016cited by this paper
• Biotechnological and biomedical applications of mesenchymal stem cells as a therapeutic system

  2016cited by this paper
• Carnitine palmitoyltransferase 1C: From cognition to cancer.

  2016cited by this paper
• Genetic alterations in fatty acid transport and metabolism genes are associated with metastatic progression and poor prognosis of human cancers

  2016cited by this paper
• Mutation in CPT1C Associated With Pure Autosomal Dominant Spastic Paraplegia.

  2015cited by this paper
• Functional consequences of glucose and oxygen deprivation on engineered mesenchymal stem cell-based cartilage constructs.

  2015cited by this paper
• Faculty Opinions recommendation of Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics.

  2015cited by this paper
• Novel Regulation of the Synthesis of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Subunit GluA1 by Carnitine Palmitoyltransferase 1C (CPT1C) in the Hippocampus*

  2015cited by this paper
• Effect of Fatty Acids on Human Bone Marrow Mesenchymal Stem Cell Energy Metabolism and Survival

  2015cited by this paper
• Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics.

  2015cited by this paper
• The structure of phosphoinositide phosphatases: Insights into substrate specificity and catalysis.

  2015cited by this paper
• Concise Reviews: Can Mesenchymal Stromal Cells Differentiate into Corneal Cells? A Systematic Review of Published Data

  2015cited by this paper
• Pericytes, mesenchymal stem cells and their contributions to tissue repair.

  2015cited by this paper
• Human mesenchymal stem cells/multipotent stromal cells consume accumulated autophagosomes early in differentiation

  2014cited by this paper
• PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation

  2014cited by this paper
• Expression of the autophagy substrate SQSTM1/p62 is restored during prolonged starvation depending on transcriptional upregulation and autophagy-derived amino acids

  2014cited by this paper
• Autophagic control of cell ‘stemness’

  2013cited by this paper
• Autophagosomes form at ER–mitochondria contact sites

  2013cited by this paper
• Cell Survival during Complete Nutrient Deprivation Depends on Lipid Droplet-fueled β-Oxidation of Fatty Acids*

  2013cited by this paper
• Autophagy in stem cells

  2013cited by this paper
• Depletion of the novel p53-target gene carnitine palmitoyltransferase 1C delays tumor growth in the neurofibromatosis type I tumor model

  2013cited by this paper
• arnitine palmitoyltransferase 1 C deficiency causes motor mpairment and hypoactivity

  2013cited by this paper
• Glucose-starved Cells Do Not Engage in Prosurvival Autophagy*

  2013cited by this paper
• Omegasomes: PI3P platforms that manufacture autophagosomes.

  2013cited by this paper
• Hypothalamic Ceramide Levels Regulated by CPT1C Mediate the Orexigenic Effect of Ghrelin

  2013cited by this paper
• The enhancement of osteogenesis through the use of dental pulp pluripotent stem cells in 3D.

  2012cited by this paper
• Dental pulp of the third molar: a new source of pluripotent-like stem cells

  2012cited by this paper
• Basal Autophagy Decreased During the Differentiation of Human Adult Mesenchymal Stem Cells

  2012cited by this paper
• Ceramide Levels Regulated by Carnitine Palmitoyltransferase 1C Control Dendritic Spine Maturation and Cognition*

  2012cited by this paper
• Carnitine palmitoyltransferase 1C promotes cell survival and tumor growth under conditions of metabolic stress.

  2011cited by this paper
• Autophagy: for better or for worse

  2011cited by this paper
• Malonyl-CoA mediates leptin hypothalamic control of feeding independent of inhibition of CPT-1a.

  2011cited by this paper
• For better or worse?

  2010cited by this paper
• Coenzyme A and its thioester pools in fasted and fed rat tissues.

  2010cited by this paper
• CPT1c Is Localized in Endoplasmic Reticulum of Neurons and Has Carnitine Palmitoyltransferase Activity*

  2008cited by this paper
• Regulation of food intake and energy expenditure by hypothalamic malonyl-CoA

  2008cited by this paper
• Brain‐specific carnitine palmitoyl‐transferase‐1c: role in CNS fatty acid metabolism, food intake, and body weight

  2008cited by this paper
• CPT I overexpression protects L6E9 muscle cells from fatty acid-induced insulin resistance.

  2007cited by this paper
• Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement.

  2006cited by this paper
• The brain-specific carnitine palmitoyltransferase-1c regulates energy homeostasis.

  2006cited by this paper
• A role for the malonyl-CoA/long-chain acyl-CoA pathway of lipid signaling in the regulation of insulin secretion in response to both fuel and nonfuel stimuli.

  2004cited by this paper
• A novel brain-expressed protein related to carnitine palmitoyltransferase I.

  2002cited by this paper
• Stem cells

  2001cited by this paper
• The malonyl-CoA-long-chain acyl-CoA axis in the maintenance of mammalian cell function.

  1999cited by this paper
• Topological and functional analysis of the rat liver carnitine palmitoyltransferase 1 expressed in Saccharomyces cerevisiae

  1998cited by this paper
• Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector.

  1996cited by this paper
• EXPRESSION OF

  year unknowncited by this paper
• Cellular Neuroscience Original Research Article Ampar Interacting Protein Cpt1c Enhances Surface Expression of Glua1-containing Receptors

  year unknowncited by this paper

• Fenofibrate targets PPARα-CPT1C axis to reverse aging by regulating lipid metabolism and mitochondrial function.

  2026cites this paper
• International Union of Basic and Clinical Pharmacology: Fundamental insights and clinical relevance regarding the carnitine palmitoyltransferase family of enzymes.

  2025cites this paper
• Fatty acid metabolic reprogramming in the tumor microenvironment: Unraveling mechanisms and therapeutic prospects

  2025cites this paper
• Exploration of Genes Related to Intramuscular Fat Deposition in Xinjiang Brown Cattle

  2024cites this paper
• Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival

  2024cites this paper
• RREB1 regulates neuronal proteostasis and the microtubule network

  2024cites this paper
• APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition

  2024cites this paper
• Synergistic Effect of Salinomycin With Budesonide on TNBC Regression via EMT Reversal and Autophagy Induction

  2024cites this paper
• The Role of the CPT Family in Cancer: Searching for New Therapeutic Strategies

  2024cites this paper
• To be or not to be a fat burner, that is the question for cpt1c in cancer cells

  2023cites this paper
• Acyl-Carnitines Exert Positive Effects on Mitochondrial Activity under Oxidative Stress in Mouse Oocytes: A Potential Mechanism Underlying Carnitine Efficacy on PCOS

  2023cites this paper
• Clonal and Scalable Endothelial Progenitor Cell Lines from Human Pluripotent Stem Cells

  2023cites this paper
• Interplay of energy metabolism and autophagy

  2023cites this paper
• Cascade-Responsive 2-DG Nanocapsules Encapsulate aV-siCPT1C Conjugates to Inhibit Glioblastoma through Multiple Inhibition of Energy Metabolism.

  2023cites this paper
• Cpt1c Downregulation Causes Plasma Membrane Remodelling and Anthracycline Resistance in Breast Cancer

  2023cites this paper
• Re-routing Metabolism by the Mitochondrial Pyruvate Carrier Inhibitor MSDC-0160 Attenuates Neurodegeneration in a Rat Model of Parkinson’s Disease

  2022cites this paper
• Hypoxia-induced mitophagy regulates proliferation, migration and odontoblastic differentiation of human dental pulp cells through FUN14 domain-containing 1

  2022cites this paper
• Identification of hub genes regulating the cell activity and function of adipose-derived stem cells under oxygen-glucose deprivation

  2022cites this paper
• Lipid Droplets and Their Autophagic Turnover via the Raft-Like Vacuolar Microdomains

  2021cites this paper
• Autophagy in tooth: Physiology, disease and therapeutic implication

  2021cites this paper
• Harnessing the Benefits of Endogenous Hydrogen Sulfide to Reduce Cardiovascular Disease

  2021cites this paper
• Effect of AMPK pathway on apoptosis of human thyroid papillary cancer B-CPAP cells under low glucose and hypoxia conditions through CPT1c regulated by PPARα

  2020cites this paper
• Schisandra Fruit Vinegar Lowers Lipid Profile in High-Fat Diet Rats

  2020cites this paper
• Sensing of nutrients by CPT1C controls SAC1 activity to regulate AMPA receptor trafficking

  2020cites this paper
• AMPK-Dependent Mechanisms but Not Hypothalamic Lipid Signaling Mediates GH-Secretory Responses to GHRH and Ghrelin

  2020cites this paper
• Carnitine palmitoyltransferase 1C contributes to progressive cellular senescence

  2020cites this paper
• Carnitine palmitoyltransferase 1C reverses cellular senescence of MRC‐5 fibroblasts via regulating lipid accumulation and mitochondrial function

  2020cites this paper
• Carnitine

  2020cites this paper
• A novel HSP90 inhibitor targeting the C-terminal domain attenuates trastuzumab resistance in HER2-positive breast cancer

  2020cites this paper
• Modulating autophagy in mesenchymal stem cells effectively protects against hypoxia- or ischemia-induced injury

  2019cites this paper
• Lipid Droplets and the Management of Cellular Stress

  2019cites this paper
• Rasal2 suppresses breast cancer cell proliferation modulated by secretory autophagy

  2019cites this paper
• The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy

  2019cites this paper
• AMPK: An Epigenetic Landscape Modulator

  2018cites this paper
• Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

  2018influential citation