Bradley 2018 Biochim Biophys Acta
| Bradley RM, Bloemberg D, Aristizabal Henao JJ, Hashemi A, Mitchell AS, Fajardo VA, Bellissimo C, Mardian EB, Bombardier E, Parรฉ MF, Moes KA, Stark KD, Tupling AR, Quadrilatero J, Duncan RE (2018) Lpaatฮด/Agpat4 deficiency impairs maximal force contractility in soleus and alters fiber type in extensor digitorum longus muscle. Biochim Biophys Acta 1863:700-11. |
Bradley RM, Bloemberg D, Aristizabal Henao JJ, Hashemi A, Mitchell AS, Fajardo VA, Bellissimo C, Mardian EB, Bombardier E, Pare MF, Moes KA, Stark KD, Tupling AR, Quadrilatero J, Duncan RE (2018) Biochim Biophys Acta
Abstract: Lysophosphatidic acid acyltransferase (LPAAT) ฮด/acylglycerophosphate acyltransferase 4 is a mitochondrial enzyme and one of five homologues that catalyze the acyl-CoA-dependent synthesis of phosphatidic acid (PA) from lysophosphatidic acid. We studied skeletal muscle LPAATฮด and found highest levels in soleus, a red oxidative fibre-type that is rich in mitochondria, and lower levels in extensor digitorum longus (EDL) (white glycolytic) and gastrocnemius (mixed fibre-type). Using Lpaatฮด-deficient mice, we found no change in soleus or EDL mass, or in treadmill time-to-exhaustion compared to wildtype littermates. There was, however, a significant reduction in the proportion of type I and type IIA fibres in EDL but, surprisingly, not soleus, where these fibre-types predominate. Also unexpectedly, there was no impairment in force generation by EDL, but a significant reduction by soleus. Oxidative phosphorylation and activity of complexes I, Iโฏ+โฏII, III, and IV in soleus mitochondria was unchanged and therefore could not explain this effect. However, pyruvate dehydrogenase activity was significantly reduced in Lpaatฮด-/- soleus and EDL. Analysis of cellular lipids indicated no difference in soleus triacylglycerol, but specific elevations in soleus PA and phosphatidylethanolamine levels, likely due to a compensatory upregulation of Lpaatฮฒ and Lpaatฮต in Lpaatฮด-/- mice. An anabolic effect for PA as an activator of skeletal muscle mTOR has been reported, but we found no change in serine 2448 phosphorylation, indicating reduced soleus force generation is unlikely due to the loss of mTOR activation by a specific pool of LPAATฮด-derived PA. Our results identify an important role for LPAATฮด in soleus and EDL. โข Keywords: Acylglycerophosphate acyltransferase (AGPAT) 4, Lysophosphatidic acid acyltransferase (LPAAT) delta, Mitochondria, Phosphatidic acid, Skeletal muscle โข Bioblast editor: Kandolf G โข O2k-Network Lab: CA Waterloo Joseph JW
Labels: MiParea: Respiration, Genetic knockout;overexpression
Organism: Mouse
Tissue;cell: Skeletal muscle
Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET
Pathway: N, S, CIV, NS
HRR: Oxygraph-2k
Labels, 2018-05
