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Mitochondrial NDUFA...
Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force
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- Liu, Zhengye (författare)
- Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden
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- Chaillou, Thomas, 1985- (författare)
- Örebro universitet,Institutionen för hälsovetenskaper,Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden
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- Santos Alves, Estela (författare)
- Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden
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- Mader, Theresa (författare)
- Karolinska Institutet
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- Jude, Baptiste (författare)
- Karolinska Institutet
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- Ferreira, Duarte M. S. (författare)
- Karolinska Institutet
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- Hynynen, Heidi (författare)
- Department of Physiology and Pharmacology, Molecular and Cellular Exercise Physiology, Karolinska Institutet, Stockholm, Sweden
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- Cheng, Arthur J. (författare)
- Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden
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- Jonsson, William O. (författare)
- Department of Physiology and Pharmacology, Molecular Muscle Physiology and Pathophysiology, Karolinska Institutet, Stockholm, Sweden
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- Pironti, Gianluigi (författare)
- Karolinska Institutet
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- Andersson, Daniel C. (författare)
- Karolinska Institutet
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- Kenne, Ellinor (författare)
- Karolinska Institutet
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- Ruas, Jorge L. (författare)
- Karolinska Institutet
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- Tavi, Pasi (författare)
- A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
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- Lanner, Johanna T. (författare)
- Karolinska Institutet
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(creator_code:org_t)
- John Wiley & Sons, 2021
- 2021
- Engelska.
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Ingår i: The FASEB Journal. - : John Wiley & Sons. - 0892-6638 .- 1530-6860. ; 35:12
- Relaterad länk:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD(+) levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ec-topically expressed NDUFA4L2 caused a similar to 20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD(+), which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
Nyckelord
- mitochondria
- muscle mass
- NDUFA4L2
- skeletal muscle
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- art (ämneskategori)
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- Av författaren/redakt...
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Liu, Zhengye
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Chaillou, Thomas ...
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Santos Alves, Es ...
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Mader, Theresa
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Jude, Baptiste
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Ferreira, Duarte ...
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visa fler...
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Hynynen, Heidi
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Cheng, Arthur J.
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Jonsson, William ...
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Pironti, Gianlui ...
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Andersson, Danie ...
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Kenne, Ellinor
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Ruas, Jorge L.
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Tavi, Pasi
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Lanner, Johanna ...
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- Av lärosätet
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Örebro universitet
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Karolinska Institutet