Acylglycerol kinase, mitochondrial (AGK)

Acylglycerol kinase, mitochondrial (AGK), is a mitochondrial membrane lipid kinase that catalyzes the phosphorylation of monoacylglycerol and diacylglycerol, generating lysophosphatidic acid and phosphatidic acid—bioactive lipids important for phospholipid metabolism and signal transduction[1][2][3]. Beyond its enzymatic role, AGK also functions structurally as a subunit of the mitochondrial TIM22 protein import complex, facilitating assembly of multispanning carrier proteins essential for mitochondrial homeostasis. Mutations in AGK cause mitochondrial DNA depletion syndrome 10, also known as Sengers syndrome, which features congenital cataracts, hypertrophic cardiomyopathy, skeletal myopathy, and lactic acidosis[1][2]. AGK is overexpressed in several cancers and plays a key role in oncogenic signaling through interactions with the JAK2/STAT3 pathway, PI3K/AKT, NF-κB, and YAP1/TEAD, promoting cell proliferation, angiogenesis, resistance to apoptosis, and tumor progression[2][3]. Targeting AGK therapeutically is being explored, but its indispensable roles in mitochondrial function and cellular metabolism present significant challenges for drug development and safety[2][3].

Other names

Acylglycerol kinaseAGKMULKhAGKHsMuLKMuLKMulti-substrate lipid kinaseFLJ10842Multiple substrate lipid kinaseCATC5CTRCT38MTDPS10

In cancer, therapeutic strategies might involve inhibition of AGK-mediated lipid kinase activity to suppress lysophosphatidic acid signaling, interference with JAK2/STAT3 and PI3K/AKT signaling cascades, or indirect suppression through microRNA modulation.