Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischemia

Kerr, Matthew; Dennis, Kaitlyn M.J.H.; Carr, Carolyn A.; Fuller, William; Berridge, G.; Röhling, S; Aitken, Connie L.; Lopez, Colleen A.; Fischer, Román; Miller, Jack J.; Clarke, Kieran; Tyler, Damian J; Heather, Lisa C.

doi:10.1096/fj.202100394r

Cited by 4 publications

(3 citation statements)

References 50 publications

(96 reference statements)

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“…This is accompanied by an acute upregulation of glycolysis to generate anaerobic ATP (251,252). However, this compensation is insufficient to maintain overall cellular energetics (253), so that cardiac function is rapidly impaired.…”

Section: Ischemia-reperfusion Of the Rodent Heartmentioning

confidence: 99%

CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease

Glatz,

Heather,

Luiken

2024

Physiological Reviews

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The multifunctional membrane glycoprotein CD36 is expressed in different types of cells and plays a key regulatory role in cellular lipid metabolism. CD36 facilitates the cellular uptake of long-chain fatty acids, mediates lipid signaling, and regulates storage and oxidation of lipids in various tissues with active lipid metabolism. CD36 deficiency leads to marked impairments in peripheral lipid metabolism, which consequently impacts on the cellular utilization of multiple different fuels, due to the integrated nature of metabolism. The functional presence of CD36 at the plasma membrane is regulated by its reversible subcellular recycling from and to endosomes, and is under the control of mechanical, hormonal and nutritional factors. Aberrations in this dynamic role of CD36 are causally associated with various metabolic diseases, in particular insulin resistance, diabetic cardiomyopathy, and cardiac hypertrophy. Recent research in cardiac muscle has disclosed the endosomal proton pump v-ATPase as a key enzyme regulating subcellular CD36 recycling and being the site of interaction between various substrates to determine cellular substrate preference. In addition, evidence is accumulating that interventions targeting CD36 directly or modulating its subcellular recycling are effective for the treatment of metabolic diseases. In conclusion, subcellular CD36 localization is the major adaptive regulator of cellular uptake and metabolism of long-chain fatty acids, and appears a suitable target for metabolic modulation therapy to mend failing hearts.

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Section: Ischemia-reperfusion Of the Rodent Heartmentioning

confidence: 99%

CD36 as a gatekeeper of myocardial lipid metabolism and therapeutic target for metabolic disease

Glatz,

Heather,

Luiken

2024

Physiological Reviews

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“…PCoA can also limit the shuttle of ADP and ATP on the mitochondrial membrane by inhibiting the activity of ADP/ATP carriers on the mitochondrial membrane 76 77 . However, during ischemia, ATP can be prevented from entering mitochondria for hydrolysis, which is a protective mechanism during ischemia 78 . However, in diabetes, the protective membrane potential of PCoA is inhibited, leading to increased ATP hydrolysis rate in diabetic heart during ischemia 78 .…”

Section: Long-chain Acyl-coamentioning

confidence: 99%

“…However, during ischemia, ATP can be prevented from entering mitochondria for hydrolysis, which is a protective mechanism during ischemia 78 . However, in diabetes, the protective membrane potential of PCoA is inhibited, leading to increased ATP hydrolysis rate in diabetic heart during ischemia 78 .…”

Section: Long-chain Acyl-coamentioning

confidence: 99%

Effects of Lipid Overload on Heart in Metabolic Diseases

Xie

Ding

et al. 2021

Horm Metab Res

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Metabolic diseases are often associated with lipid and glucose metabolism abnormalities, which increase the risk of cardiovascular disease. Diabetic cardiomyopathy (DCM) is an important development of metabolic diseases and a major cause of death. Lipids are the main fuel for energy metabolism in the heart. The increase of circulating lipids affects the uptake and utilization of fatty acids and glucose in the heart, and also affects mitochondrial function. In this paper, the mechanism of lipid overload in metabolic diseases leading to cardiac energy metabolism disorder is discussed.

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