Acylglycerol Kinase-Targeted Therapies in Oncology

Chu, Binxiang; Hong, Zhenghua; Zheng, Xiongwei

doi:10.3389/fcell.2021.659158

Cited by 7 publications

(7 citation statements)

References 67 publications

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“…Moreover AGK (acylglycerol kinase) protein, a central cluster node evidenced by the PPI network analysis (Figure 2), is involved in the metabolism of mitochondrial phospholipids and in the stability of SLC25A4 (ADP/ATP translocase 1). Interesting, SLC25A4 knockout mice exhibit phenotypes of hypertrophic cardiomyopathy, exercise intolerance, and lacticacidemia [53]. USP49, another PPI network central node, is involved in splicing alterations as it is essential for the cotranscriptional splicing [54].…”

Section: Discussionmentioning

confidence: 99%

Circulating Transcriptional Profile Modulation in Response to Metabolic Unbalance Due to Long-Term Exercise in Equine Athletes: A Pilot Study

Cappelli

Mecocci

Capomaccio

et al. 2021

Genes

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Physical exercise has been associated with the modulation of micro RNAs (miRNAs), actively released in body fluids and recognized as accurate biomarkers. The aim of this study was to measure serum miRNA profiles in 18 horses taking part in endurance competitions, which represents a good model to test metabolic responses to moderate intensity prolonged efforts. Serum levels of miRNAs of eight horses that were eliminated due to metabolic unbalance (Non Performer-NP) were compared to those of 10 horses that finished an endurance competition in excellent metabolic condition (Performer-P). Circulating miRNA (ci-miRNA) profiles in serum were analyzed through sequencing, and differential gene expression analysis was assessed comparing NP versus P groups. Target and pathway analysis revealed the up regulation of a set of miRNAs (of mir-211 mir-451, mir-106b, mir-15b, mir-101-1, mir-18a, mir-20a) involved in the modulation of myogenesis, cardiac and skeletal muscle remodeling, angiogenesis, ventricular contractility, and in the regulation of gene expression. Our preliminary data open new scenarios in the definition of metabolic adaptations to the establishment of efficient training programs and the validation of athletes’ elimination from competitions.

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Section: Discussionmentioning

confidence: 99%

Circulating Transcriptional Profile Modulation in Response to Metabolic Unbalance Due to Long-Term Exercise in Equine Athletes: A Pilot Study

Cappelli

Mecocci

Capomaccio

et al. 2021

Genes

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“…AGK is located within the IMM and has two known functions: it is a phospholipid kinase that synthesizes phosphatidic acid, a precursor of CL, and a component of the membrane translocase complex TIM22, which mediates the import of mitochondrial membrane proteins that are synthesized in the cytosol. This moonlight function of AGK might explain the wide spectrum of mitochondrial abnormalities observed in Sengers syndrome [ 89 , 90 ]. One prominent defect is decreased activity of the mitochondrial adenine nucleotide translocator (ANT1), which was initially considered the primary cause of the disease.…”

Section: Disorders Caused By Defective Cardiolipin Remodellingmentioning

confidence: 99%

Cardiac Involvement in Mitochondrial Disorders

Popoiu

Dudek

Maack

et al. 2023

Curr Heart Fail Rep

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Purpose of Review We review pathophysiology and clinical features of mitochondrial disorders manifesting with cardiomyopathy. Recent Findings Mechanistic studies have shed light into the underpinnings of mitochondrial disorders, providing novel insights into mitochondrial physiology and identifying new therapeutic targets. Summary Mitochondrial disorders are a group of rare genetic diseases that are caused by mutations in mitochondrial DNA (mtDNA) or in nuclear genes that are essential to mitochondrial function. The clinical picture is extremely heterogeneous, the onset can occur at any age, and virtually, any organ or tissue can be involved. Since the heart relies primarily on mitochondrial oxidative metabolism to fuel contraction and relaxation, cardiac involvement is common in mitochondrial disorders and often represents a major determinant of their prognosis.

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“…The AGK protein consists of a typical two-domain fold (DGK domain 1 and DGK domain 2) that mediates phosphorylation of monoacylglycerols or diacylglycerols and has an N-terminal α1 helix that anchors to the membrane and a C-terminal key region with an additional membrane anchor helix loop (Figure 2) [6,21].…”

Section: Agk Protein Modelingmentioning

confidence: 99%

“…Mitochondrial diseases can arise due to defects in nuclear or mitochondrial DNA (nDNA and mtDNA, respectively) genes that encode proteins required for normal mitochondrial structure and/or function [5]. Acylglycerol kinase (AGK) is a mitochondrial membrane protein involved not only in lipid and glycerolipid metabolism but also in mitochondrial protein transport, glycolysis, and thrombocytopoiesis [6][7][8]. AGK can act as a lipid kinase to catalyze the phosphorylation of diacylglycerol (DAG) and monoacylglycerol (MAG) to phosphatidic acid (PA) and lysophosphatidic acid (LPA), respectively.…”

Section: Introductionmentioning

confidence: 99%

Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome

Gouveia

Vázquez-Mosquera

Hermida‐Ameijeiras

et al. 2021

IJMS

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Mitochondrial functional integrity depends on protein and lipid homeostasis in the mitochondrial membranes and disturbances in their accumulation can cause disease. AGK, a mitochondrial acylglycerol kinase, is not only involved in lipid signaling but is also a component of the TIM22 complex in the inner mitochondrial membrane, which mediates the import of a subset of membrane proteins. AGK mutations can alter both phospholipid metabolism and mitochondrial protein biogenesis, contributing to the pathogenesis of Sengers syndrome. We describe the case of an infant carrying a novel homozygous AGK variant, c.518+1G>A, who was born with congenital cataracts, pielic ectasia, critical congenital dilated myocardiopathy, and hyperlactacidemia and died 20 h after birth. Using the patient’s DNA, we performed targeted sequencing of 314 nuclear genes encoding respiratory chain complex subunits and proteins implicated in mitochondrial oxidative phosphorylation (OXPHOS). A decrease of 96-bp in the length of the AGK cDNA sequence was detected. Decreases in the oxygen consumption rate (OCR) and the OCR:ECAR (extracellular acidification rate) ratio in the patient’s fibroblasts indicated reduced electron flow through the respiratory chain, and spectrophotometry revealed decreased activity of OXPHOS complexes I and V. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts and describe the possible molecular mechanism underlying the pathogenicity of this novel AGK variant. Experimental validation using in vitro analysis allowed an accurate characterization of the disease-causing variant.

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Acylglycerol Kinase-Targeted Therapies in Oncology

Cited by 7 publications

References 67 publications

Circulating Transcriptional Profile Modulation in Response to Metabolic Unbalance Due to Long-Term Exercise in Equine Athletes: A Pilot Study

Circulating Transcriptional Profile Modulation in Response to Metabolic Unbalance Due to Long-Term Exercise in Equine Athletes: A Pilot Study

Cardiac Involvement in Mitochondrial Disorders

Characterization of a Novel Splicing Variant in Acylglycerol Kinase (AGK) Associated with Fatal Sengers Syndrome

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