Abstract
The endoplasmic reticulum (ER) and mitochondria are essential intracellular organelles that actively communicate via temporally and spatially formed contacts called mitochondria-associated membranes (MAMs). These mitochondria-ER contacts are not only necessary for the physiological function of the organelles and their coordination with each other, but they also control the intracellular lipid exchange, calcium signaling, cell survival, and homeostasis in cellular metabolism. Growing evidence strongly supports the role of the mitochondria-ER connection in the insulin resistance of peripheral tissues, pancreatic β cell dysfunction, and the consequent development of type 2 diabetes mellitus (T2DM). In this review, we summarize current advances in the understanding of the mitochondria-ER connection and specifically focus on addressing a new perspective of the alterations in mitochondria-ER communication in insulin signaling and β cell maintenance.
Highlights
type 2 diabetes mellitus (T2DM) is the most common endocrine and metabolic disorder in humans, and it has increased dramatically in the past 20 years
It is well-known that the redox state at the mitochondria-associated endoplasmic reticulum membranes (MAM) modulates the activity of the MAM-enriched protein ER oxidoreductin-1 (Ero1)-α (Fan and Simmen, 2019), which mediates the formation of hydrogen peroxide (H2O2) and, in turn, potentiates Ca2+ signaling at the MAM and the consequent oxidation of the inositol 1 (IP3Rs) (Anelli et al, 2012)
Some MAM-enriched enzymes are essential for the synthesis of lipids. These enzymes include the long-chain fatty acidCoA ligase 4 (FACL4/ACS4) that activates long-chain fatty acids for the synthesis of complex lipids or acylated proteins (Lewin et al, 2001), stearoyl-CoA desaturase-1 (SCD1) that catalyzes the biosynthesis of monounsaturated fatty acids from saturated substrates (Man et al, 2006), diacylglycerol acyltransferase 2 (DGAT2) that catalyzes the final step of triacylglycerol synthesis (Stone et al, 2009), and acyl-coenzyme-A-cholesterol acyltransferase 1 (ACAT1)/SOAT1 that converts intracellular free cholesterol into cholesteryl ester (Rusinol et al, 1994)
Summary
The endoplasmic reticulum (ER) and mitochondria are essential intracellular organelles that actively communicate via temporally and spatially formed contacts called mitochondria-associated membranes (MAMs). These mitochondria-ER contacts are necessary for the physiological function of the organelles and their coordination with each other, but they control the intracellular lipid exchange, calcium signaling, cell survival, and homeostasis in cellular metabolism. Growing evidence strongly supports the role of the mitochondria-ER connection in the insulin resistance of peripheral tissues, pancreatic β cell dysfunction, and the consequent development of type 2 diabetes mellitus (T2DM).
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