Skip to main content
Fig. 4 | Lipids in Health and Disease

Fig. 4

From: Mutual interaction between endoplasmic reticulum and mitochondria in nonalcoholic fatty liver disease

Fig. 4

ERS and oxidative stress in patients with NAFLD and the generation and crosstalk of ROS signalling connecting these pathways. Excess accumulation of FFAs in hepatocytes induces ERS and oxidative stress, both of which are linked by ROS and Ca2+. a) When the UPR reaction fails to solve protein errors or unfolding, the ERS response may be delayed or insufficient, and hepatocyte apoptosis may be induced by ER and mitochondrial stress responses or other independent pathways. b) ROS and oxidative stress disrupt ER function, and Ca2+ release from the ER depends on ROS. Excess Ca2+ induces OMM permeabilization, which in turn increases mitochondrial ROS release. The increases in ROS levels will further increase intracellular Ca2+ levels. c) In this complex situation, ERS can induce apoptosis through a number of mechanisms, including mitochondrial damage leading to the production of apoptotic factors, cytochrome release, apoptotic body formation, and sequential activation of caspase-9 and caspase-3. IRE-1 recruits TRAF-2 to activate ASK-1 and JNK in a potential proapoptotic pathway that is further maintained by ROS or caspase-12. Activation of PERK and ATF6 (p90) leads to activation of ATF4 and ATF6, respectively (nuclear translocation of p50), and upregulation of CHOP expression, which inhibits Bcl-2 expression and promotes apoptosis

Back to article page