Fig. 2

Pathological states and associated hepatic metabolic diseases resulting from disruption of the structural and functional integrity of MAMs. Mitochondria and the ER intersect functionally and structurally in areas that researchers call MAMs. Many mitochondrial and ER-related proteins or signalling molecules are located here. The structural and functional integrity of MAMs determines the normal communication between the ER and mitochondria. Damage to the integrity of MAMs, including changes in the levels of membrane proteins (increases or decreases) and suboptimal spacing of MAMs (too close or too far), can lead to miscommunication between the organelles, which can directly or indirectly lead to hepatic ERS, oxidative stress and imbalanced Ca²⁺ homeostasis. When these hepatocyte problems are amplified, glucose and lipid metabolism disturbances, chronic inflammation and IR develop. T2DM, NAFLD, and other metabolic diseases occur or develop when mechanisms in the body are insufficient to counteract these dangerous pathological reactions. Therefore, ER–mitochondria miscommunication is involved in the pathophysiology of T2DM and NAFLD