Table 1 The roles and mechanisms of GPDs in diverse pathologies.
From: Glycerol 3-phosphate dehydrogenases (1 and 2) in cancer and other diseases
Gene | Disease | Tissue | Implication | Mechanism | Ref. |
|---|---|---|---|---|---|
GPD1 | Obesity | Adipose | Pro-obesity | Generates G3P leading to an increase in TG accumulation | |
Muscle | Fatty acid oxidation in skeletal muscle | Possibly regulated by EID1 | |||
Transient infantile hypertriglyceridemia | Liver | Mutation of GPD1 associated with TG secretion | Regulation of DHAP and fatty acid oxidation | ||
Neuroinflammation | Brain | Low GPD1 activity in brain contributes to neuronal susceptibility to mitochondrial complex I dysfunction | GPD1 overexpression regenerates NAD+ and enhances G3P synthesis in complex I-compromised conditions | ||
N/A | In vitro cell line | Antioxidant | Unknown | ||
GPD1L | Brugada syndrome | Heart | GPD1L mutation associated with Brugada syndrome and cardiac sudden death | Association with SCN5A, altering inward sodium current in the heart | |
GPD2 | Obesity | Adipose | BAT thermogenesis | Unknown | |
Muscle | Muscle regeneration and myoblast differentiation | Increases NAD+/NADH and activates AMPK/PGC1a resulting in mitochondrial biogenesis | |||
Diabetes | Pancreas | Implicates in glucose-mediated insulin secretion | Altering glycolysis activity through NAD+/NADH shuttling | ||
Kidney | Protects podocytes | Inhibits RAGE pathway, enhancing mitochondrial biogenesis/metabolism and lowering ROS | |||
Steatosis | Liver | GPD2 loss leads to ER-stress-induced steatosis | Induction of ubiquitin-mediated degradation of cyclophilin D that activates PTP, altering mitochondrial calcium release | ||
N/A | Brain | Suggested to be involved in neurotransmission | Unknown | ||
Inflammatory diseases | Immune system | T-cell activation | Hyper-reduction of ubiquinone, generation of ROS during TCR signaling | ||
LPS tolerance of macrophages | Boosting glucose oxidation to support acetyl-CoA for histone acetylation of inflammatory genes upon acute LPS stimulation. Induce RET and reduction in oxidative metabolism; reverse histone acetylation and macrophage activation upon prolonged LPS stimulation. | ||||
Ischemic disease | Heart | Responsible for cell death during IRI | ROS release | ||
Protection against MI | Calcium influx in MI activates GPD2 facilitating ATP synthesis from glycerol as an adaptation to the limited oxygen supply | ||||
N/A | Sperm | Acrosome reaction | ROS generation in spermatozoa |
