Interaction of activated P-JNK with mitochondrial protein SAB impairs mitochondrial respiration and produces ROS leading to amplify feed-forward activation of JNK, known as the JNK-SAB-ROS activation loop [30,51,82].

Jan 9, 2014 · Knockdown of mitochondrial Sab prevented ER stress-induced sustained JNK activation, impaired respiration, and apoptosis, but did not alter the magnitude or time course of activation of ER stress...

Using knockdown or liver specific deletion of Sab we aimed to elucidate the consequences of this interaction on mitochondrial function in isolated mitochondria and liver injury models in vivo. Respiration in isolated mitochondria was directly inhibited by P-JNK+ATP.

Mar 15, 2024 · The JNK-SAB-ROS activation loop was uncovered recently, but the importance of the loop in the regulation of various modes of cell death has not been incorporated. This review has proposed the possible involvement of JNK and SAB interaction in ferroptosis and pyroptosis.

Feb 15, 2015 · We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes.

In all three models we have identified a key role for SH3BP5 (Sab), an outer membrane mitochondrial protein which is a binding target and substrate of JNK. When JNK phosphorylates Sab, mitochondrial respiration becomes impaired and ROS release is enhanced.

Sustained c-Jun N-terminal kinase (JNK) activation has been implicated in many models of cell death and tissue injury. Phosphorylated JNK (p-JNK) interacts with the mitochondrial outer membrane SH3 homology associated BTK binding protein (Sab, or SH3BP5).

Jan 9, 2014 · In this paper, we have identified that P-JNK interaction with Sab is a key event in the perturbation of mitochondrial ATP producing respiration in tunicamycin or BFA-induced ER stress and has a major role in cell death induced by ER stress in hepatocytes and HeLa cells. Tunicamycin and BFA are widely used ER stress inducers.

Jun 1, 2015 · We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes.

KIM1 peptide blocks the interaction of JNK and Sab and has shown efficacy in preventing cardiac and brain injury in ischemia/reperfusion (11, 12). Thus, in principle, approaches to blocking the interaction of JNK and Sab show promise. Alternatively, decreasing …