PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. Issue 7 (2nd April 2019)
- Record Type:
- Journal Article
- Title:
- PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. Issue 7 (2nd April 2019)
- Main Title:
- PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice
- Authors:
- Hori, Shimpei
Hiramuki, Yosuke
Nishimura, Daigo
Sato, Fuminori
Sehara-Fujisawa, Atsuko - Abstract:
- ABSTRACT: Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self‐renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate the proliferation and differentiation of SMSCs and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes the effects of hypoxia on preferential self‐renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to the tricarboxylic acid (TCA) cycle by producing acetyl coenzyme A from pyruvate. PDH kinase 1, highly expressed under hypoxia, is down‐regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin‐deficient mouse model of Duchenne muscular dystrophy. Thus, the flow from glycolysis to the TCA cycle mediated by PDH plays a pivotal role in the differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.—Hori, S., Hiramuki, Y., Nishimura, D., Sato, F., Sehara‐Fujisawa, A. PDH‐mediated metabolic flow isABSTRACT: Skeletal muscle satellite cells (SMSCs), the major stem cells responsible for the regeneration of skeletal muscle, are normally cell cycle arrested but differentiate to generate myocytes upon muscle damage, forming new myofibers along with self‐renewing stem cells in preparation for subsequent injury. In this study, we investigated which factors stimulate the proliferation and differentiation of SMSCs and found that pyruvate, the end product of glycolysis, stimulates their differentiation. Pyruvate antagonizes the effects of hypoxia on preferential self‐renewal of SMSCs through dephosphorylation or activation of pyruvate dehydrogenase (PDH), which mediates opening of the gateway from glycolysis to the tricarboxylic acid (TCA) cycle by producing acetyl coenzyme A from pyruvate. PDH kinase 1, highly expressed under hypoxia, is down‐regulated under normoxic conditions, leading to an increase in dephosphorylated PDH. Conditional deletion of PDH in SMSCs affects cell divisions generating myocytes and subsequent myotube formation, inefficient skeletal muscle regeneration upon injury, and aggravated pathogenesis of a dystrophin‐deficient mouse model of Duchenne muscular dystrophy. Thus, the flow from glycolysis to the TCA cycle mediated by PDH plays a pivotal role in the differentiation of SMSCs, which is critical for the progression of skeletal muscle regeneration.—Hori, S., Hiramuki, Y., Nishimura, D., Sato, F., Sehara‐Fujisawa, A. PDH‐mediated metabolic flow is critical for skeletal muscle stem cell differentiation and myotube formation during regeneration in mice. FASEB J. 33, 8094–8109 (2019). www.fasebj.org … (more)
- Is Part Of:
- FASEB journal. Volume 33:Issue 7(2019)
- Journal:
- FASEB journal
- Issue:
- Volume 33:Issue 7(2019)
- Issue Display:
- Volume 33, Issue 7 (2019)
- Year:
- 2019
- Volume:
- 33
- Issue:
- 7
- Issue Sort Value:
- 2019-0033-0007-0000
- Page Start:
- 8094
- Page End:
- 8109
- Publication Date:
- 2019-04-02
- Subjects:
- satellite cell -- tissue regeneration -- cell division -- metabolic control
Biology -- Periodicals
Biology, Experimental -- Periodicals
570 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1096/fj.201802479R ↗
- Languages:
- English
- ISSNs:
- 0892-6638
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 13225.xml