TY  - JOUR
T1  - The central role of mitochondrial metabolism in hepatic steatosis
AU  - Win, Sanda
AU  - Than, Tin Aung
AU  - Kaplowitz, Neil
AU  - Wong, Nicole
AU  - Arya, Aliza
AU  - Win, Zin Thandar
AU  - Win, Shwe Hlaing
AU  - Phyu, Ei Hnin
AU  - Kuemerle, Christina
AU  - Suh, Jake
AU  - Avanesyan, Sona
AU  - Dobaria, Pujan Prakash
AU  - Lwin, Hnin Wai
AU  - Wong, Sean
AU  - Kaw, Shannon
AU  - Wong, Samuel
AU  - Soe, Kyaw Khaing
AU  - Kyaw, Garmani
AU  - Aung, Filbert Win Min
Y1  - 2024///
JO  - Exploration of Digestive Diseases
VL  - 3
IS  - 1
SP  - 42
EP  - 68
DO  - 10.37349/edd.2024.00039
UR  - https://www.explorationpub.com/Journals/edd/Article/100539
AB  - Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.
ER  -