Figure 1.

Sirt4 and its substrates in the mitochondrial metabolic pathways. Sirt4 modulates directly or indirectly the activity of several targets (depicted in yellow) that play key roles in various metabolic processes. Green arrows and red lines indicate the promotion/activation and suppression/inhibition of a specific activity, respectively. (A) Sirt4 modulation of lipid metabolism. (B) Sirt4 inhibition of PDH through lipoamidase activity. (C) Sirt4 modulation of insulin secretion and sensitivity. (D) Sirt4 effects on mitochondrial oxidative stress. (E) Sirt4 and cancer. ACC, acetyl-CoA carboxylase; Ac-CoA, acetyl coenzyme A; AMPK, AMP-activated protein kinase; ANT2, adenine nucleotide translocator 2; ATP, adenosine triphosphate; CPT1, carnitine palmitoyl-transferase 1; CtBP, C-terminal binding protein; DLAT, dihydrolipoyllysine acetyltransferase; FA, fatty acids; FAO, fatty acids oxidation; GDH, glutamate dehydrogenase; GLS, glutaminase; IDE, insulin degrading enzyme; MCCC, 3-methylcrotonyl-CoA carboxylase; MC-CoA, 3-methylcrotonyl-CoA; MGc-CoA, 3-methylglutaconyl-CoA; MCD, malonyl-CoA decarboxylase; MnSOD, manganese-dependent superoxide dismutase; mTORC1, mammalian target of rapamycin complex 1; MTPα, mitochondrial trifunctional protein α; PGC-1α, peroxisome proliferator-activated receptor gamma co-activator 1α; PDH, pyruvate dehydrogenase; PPARα, peroxisome proliferator-activated receptors α; ROS, reactive oxygen species; TCA, tri-carboxylic acid; TF, transcription factor.