Insight of the role of mitochondrial calcium homeostasis in hepatic insulin resistance

Abstract

Due to the rapid rise in the prevalence of chronic metabolic disease, more and more clinicians and basic medical researchers focus their eyesight on insulin resistance (IR), an early and central event of metabolic diseases. The occurrence and development of IR are primarily caused by excessive energy intake and reduced energy consumption. Liver is the central organ that controls glucose homeostasis, playing a considerable role in systemic IR. Decreased capacity of oxidative metabolism and mitochondrial dysfunction are being blamed as the direct reason for the development of IR. Mitochondrial Ca²⁺ plays a fundamental role in maintaining proper mitochondrial function and redox stability. The maintaining of mitochondrial Ca²⁺ homeostasis requires the cooperation of ion channels in the inner and outer membrane of mitochondria, such as mitochondrial calcium uniporter complex (MCUC) and voltage-dependent anion channels (VDACs). In addition, the crosstalk between the endoplasmic reticulum (ER), lysosome and plasma membrane with mitochondria is also significant for mitochondrial calcium homeostasis, which is responsible for an efficient network of cellular Ca²⁺ signaling. Here, we review the recent progression in the research about the regulation factors for mitochondrial Ca²⁺ and how the dysregulation of mitochondrial Ca²⁺ homeostasis is involved in the pathogenesis of hepatic IR, providing a new perspective for further exploring the role of ion in the onset and development of IR.

Keywords: Hepatic insulin resistance; Lysosomal calcium; Mitochondria-associated ER membranes; Mitochondrial calcium; Redox system.