Control by Ca2+ of mitochondrial structure and function in pancreatic β-cells. (November 2020)

• Record Type: Journal Article
• Authors: Georgiadou, Eleni; Rutter, Guy A.
• Is Part Of: Cell calcium. Volume 91(2020)
• Publication Date: 2020-11
• Subjects: [Ca2+]cyt [Ca2+]mt, free cytosolic and intramitochondrial Ca2+ respectively -- IMM OMM inner and outer mitochondrial membrane, Δψm, mitochondrial membrane potential -- GSIS glucose-stimulated insulin secretion -- KATP channels ATP-sensitive potassium channels -- VDCCs voltage-dependent-calcium channels -- MCU mitochondrial Ca2+ uniporter -- mPTP mitochondrial permeability transition pore -- NCLX mitochondrial Na+/Ca2+ exchanger -- Mfn1/2 mitofusin 1/2 -- mtDNA mitochondrial DNA -- T2D type 2 diabetes; Type 2 diabetes -- Mitochondria -- Ca2+ -- β-cells -- Insulin secretion; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2020.102282
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: A reduction in mitochondrial Ca 2+ uptake through altered Mcu expression or impairment of the mitochondrial fusion and fission machinery may be potential pathways towards β-cell failure in type 2 diabetes. Highlights: Mitochondrial Ca 2+ uptake is essential for normal β-cell function and insulin secretion. Changes in mitochondrial ultrastructure are observed in type 2 diabetes and may be driven by altered Ca 2+ homeostasis. mtDNA mutations lead to impaired GSIS and diabetes in rodents and humans. Abstract: Mitochondria play a central role in glucose metabolism and the stimulation of insulin secretion from pancreatic β-cells. In this review, we discuss firstly the regulation and roles of mitochondrial Ca 2+ transport in glucose-regulated insulin secretion, and the molecular machinery involved. Next, we discuss the evidence that mitochondrial dysfunction in β-cells is associated with type 2 diabetes, from a genetic, functional and structural point of view, and then the possibility that these changes may in part be mediated by dysregulation of cytosolic Ca 2+ . Finally, we review the importance of preserved mitochondrial structure and dynamics for mitochondrial gene expression and their possible relevance to the pathogenesis of type 2 diabetes.