Mitochondrial P2X7 receptor localization modulates energy metabolism enhancing physical performance

Abstract Basal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, ATP synthesis and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack a) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca2+ level, b) modifies expression pattern of oxidative phosphorylation (OxPhos) enzymes, and c) severely affects cardiac performance. Hearts from P2rx7-deleted versus WT mice are larger, heart mitochondria smaller, and stroke volume (SV), ejection fraction (EF), fractional shortening (FS) and cardiac output (CO), are significantly decreased. Accordingly, physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.

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The P2X7 receptor localizes to the mitochondria, modulates mitochondrial energy metabolism and enhances physical performance

10.1101/2020.09.18.303511 ◽

2020 ◽

Author(s):

Alba Clara Sarti ◽

Valentina Vultaggio-Poma ◽

Simonetta Falzoni ◽

Sonia Missiroli ◽

Anna Lisa Giuliani ◽

...

Keyword(s):

Energy Metabolism ◽

Physical Fitness ◽

P2x7 Receptor ◽

Human Fibroblasts ◽

Atp Synthesis ◽

Heart Tissue ◽

Mitochondrial Potential ◽

Mitochondrial Energy Metabolism ◽

Microglia Cell ◽

Basal Expression

AbstractBasal expression of the P2X7 receptor (P2X7R) improves mitochondrial metabolism, ATP synthesis and overall fitness of immune and non-immune cells. We investigated P2X7R contribution to energy metabolism and subcellular localization in fibroblasts (mouse embryo fibroblasts and HEK293 human fibroblasts), mouse microglia (primary brain microglia and the N13 microglia cell line), and heart tissue. The P2X7R localizes to mitochondria, and its lack a) decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, mitochondrial matrix Ca2+ level, b) modifies expression pattern of oxidative phosphorylation (OxPhos) enzymes, and c) severely affects cardiac performance. Hearts from P2rx7-deleted versus WT mice are larger, heart mitochondria smaller, and stroke volume (SV), ejection fraction (EF), fractional shortening (FS) and cardiac output (CO), are significantly decreased. Accordingly, physical fitness of P2X7R-null mice is severely reduced. Thus, the P2X7R is a key modulator of mitochondrial energy metabolism and a determinant of physical fitness.

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The role of Ndufb6 subunit of the electron transport system complex I in the regulation of mitochondrial energy metabolism and insulin sensitivity in C2C12 myotubes

Diabetologie und Stoffwechsel ◽

10.1055/s-0037-1601643 ◽

2017 ◽

Vol 12 (S 01) ◽

pp. S1-S84

Author(s):

T Jelenik ◽

SW Görgens ◽

N Krako Jakovljevic ◽

I Rokitta ◽

NM Lalic ◽

...

Keyword(s):

Insulin Sensitivity ◽

Energy Metabolism ◽

Electron Transport ◽

Transport System ◽

Complex I ◽

Electron Transport System ◽

C2c12 Myotubes ◽

Mitochondrial Energy Metabolism

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Therapeutic Approaches Using Riboflavin in Mitochondrial Energy Metabolism Disorders

Current Drug Targets ◽

10.2174/1389450117666160813180812 ◽

2016 ◽

Vol 17 (13) ◽

pp. 1527-1534 ◽

Cited By ~ 18

Author(s):

Bárbara J. Henriques ◽

Tânia G. Lucas ◽

Cláudio M. Gomes

Keyword(s):

Energy Metabolism ◽

Therapeutic Approaches ◽

Mitochondrial Energy Metabolism

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Mitochondrial energy metabolism is negatively regulated by cannabinoid receptor 1 in intact human epidermis

Experimental Dermatology ◽

10.1111/exd.14110 ◽

2020 ◽

Vol 29 (7) ◽

pp. 616-622 ◽

Cited By ~ 1

Author(s):

Attila Oláh ◽

Majid Alam ◽

Jérémy Chéret ◽

Nikolett Gréta Kis ◽

Zoltán Hegyi ◽

...

Keyword(s):

Energy Metabolism ◽

Cannabinoid Receptor ◽

Human Epidermis ◽

Cannabinoid Receptor 1 ◽

Mitochondrial Energy Metabolism

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Protective effects of lipoic acid against acrylamide-induced neurotoxicity: involvement of mitochondrial energy metabolism and autophagy

Food & Function ◽

10.1039/c7fo01429e ◽

2017 ◽

Vol 8 (12) ◽

pp. 4657-4667 ◽

Cited By ~ 11

Author(s):

Ge Song ◽

Zhigang Liu ◽

Luanfeng Wang ◽

Renjie Shi ◽

Chuanqi Chu ◽

...

Keyword(s):

Energy Metabolism ◽

Lipoic Acid ◽

Redox Status ◽

Protective Effects ◽

Mitochondrial Energy Metabolism

Lipoic acid (LA) suppressed acrylamide (ACR)-induced inflammation, redox status disturbance, autophagy, and apoptosis mediated by mitochondria in the SH-SY5Y cells.

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The NADH-fumarate reductase system, a novel mitochondrial energy metabolism, is a new target for anticancer therapy in tumor microenvironments

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.2010.05620.x ◽

2010 ◽

Vol 1201 (1) ◽

pp. 44-49 ◽

Cited By ~ 39

Author(s):

Eriko Tomitsuka ◽

Kiyoshi Kita ◽

Hiroyasu Esumi

Keyword(s):

Energy Metabolism ◽

Anticancer Therapy ◽

Fumarate Reductase ◽

Mitochondrial Energy Metabolism ◽

Tumor Microenvironments ◽

System A

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ConA induced changes in energy metabolism of rat thymocytes

Bioscience Reports ◽

10.1007/bf01121501 ◽

1992 ◽

Vol 12 (5) ◽

pp. 381-386 ◽

Cited By ~ 20

Author(s):

F. Buttgereit ◽

M. D. Brand ◽

M. Müller

Keyword(s):

Protein Synthesis ◽

Oxygen Consumption ◽

Energy Metabolism ◽

Dna Synthesis ◽

Atp Synthesis ◽

Proton Leak ◽

Ehrlich Ascites ◽

Activated State ◽

Ehrlich Ascites Tumour ◽

Induced Changes

The influence of ConA on the energy metabolism of quiescent rat thymocytes was investigated by measuring the effects of inhibitors of protein synthesis, proteolysis, RNA/DNA synthesis, Na+K+-ATPase, Ca2+-ATPase and mitochondrial ATP synthesis on respiration. Only about 50% of the coupled oxygen consumption of quiescent thymocytes could be assigned to specific processes using two different media. Under these conditions the oxygen is mainly used to drive mitochondrial proton leak and to provide ATP for protein synthesis and cation transport, whereas oxygen consumption to provide ATP for RNA/DNA synthesis and ATP-dependent proteolysis was not measurable. The mitogen ConA produced a persistent increase in oxygen consumption by about 30% within seconds. After stimulation more than 80% of respiration could be assigned to specific processes. The major oxygen consuming processes of ConA-stimulated thymocytes are mitochondrial proton leak, protein synthesis and Na+K+-ATPase with about 20% each of total oxygen consumption, while Ca2+-ATPase and RNA/DNA synthesis contribute about 10% each. Quiescent thymocytes resemble resting hepatocytes in that most of the oxygen consumption remains unexplained. In constrast, the pattern of energy metabolism in stimulated thymocytes is similar to that described for Ehrlich Ascites tumour cells and splenocytes, which may also be in an activated state. Most of the oxygen consumption is accounted for, so the unexplained process(es) in unstimulated cells shut(s) off on stimulation.

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