title: Contribution of mitochondria and endoplasmic reticulum dysfunction in insulin resistance: Distinct or interrelated roles?
abstract: Mitochondria and the endoplasmic reticulum (ER) regulate numerous cellular processes, and are critical contributors to cellular and whole-body homoeostasis. More important, mitochondrial dysfunction and ER stress are both closely associated with hepatic and skeletal muscle insulin resistance, thereby playing crucial roles in altered glucose homoeostasis in type 2 diabetes mellitus (T2DM). The accumulated evidence also suggests a potential interrelationship between alterations in both types of organelles, as mitochondrial dysfunction could participate in activation of the unfolded protein response, whereas ER stress could influence mitochondrial function. The fact that mitochondria and the ER are physically and functionally interconnected via mitochondria-associated membranes (MAMs) supports their interrelated roles in the pathophysiology of T2DM. However, the mechanisms that coordinate the interplay between mitochondrial dysfunction and ER stress, and its relevance to the control of glucose homoeostasis, are still unknown. This review evaluates the involvement of mitochondria and ER independently in the development of peripheral insulin resistance, as well as their potential roles in the disruption of organelle crosstalk at MAM interfaces in the alteration of insulin signalling.
authors: INSERM UMR-1060, CarMeN Laboratory, Lyon 1 University, INRA U1235, INSA of Lyon, Rockefeller and Charles-Merieux Lyon-Sud medical Universities, 69003 Lyon, France; Endocrinology, diabetology and nutrition service, Lyon-Sud Hospital, Hospices Civils de Lyon, 69310 Pierre-Bénite, France. Electronic address: jennifer.rieusset@univ-lyon1.fr.
authors: J
authors: J
authors: Rieusset
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D056811:Unfolded Protein Response
keywords: Endoplasmic reticulum; Insulin resistance; Mitochondria; Mitochondria-associated membranes; Type 2 diabetes