TY - JOUR
T1 - Adenylate kinase 1 deficiency induces molecular and structural adaptations to support muscle energy metabolism
AU - Janssen, Edwin
AU - De Groof, Ad
AU - Wijers, Mietske
AU - Fransen, Jack
AU - Dzeja, Petras P.
AU - Terzic, Andre
AU - Wieringa, Bé
PY - 2003/4/11
Y1 - 2003/4/11
N2 - Genetic ablation of adenylate kinase 1 (AK1), a member of the AK family of phosphotransfer enzymes, disturbs muscle energetic economy and decreases tolerance to metabolic stress, despite rearrangements in alternative high energy phosphoryl transfer pathways. To define the mechanisms of this adaptive response, soleus and gastrocnemius muscles from AK1-/- mice were characterized by cDNA array profiling, Western blot and ultrastructural analysis. We demonstrate that AK1 deficiency induces fiber-type specific variation in groups of transcripts involved in glycolysis and mitochondrial metabolism and in gene products defining structural and myogenic events. This was associated with increased phosphotransfer capacities of the glycolytic enzymes pyruvate kinase and 3-phosphoglycerate kinase. Moreover, in AK1-/- mice, fast-twitch gastrocnemius, but not slow-twitch soleus, had an increase in adenine nucleotide translocator (ANT) and mitochondrial creatine kinase protein, along with a doubling of the intermyofibrillar mitochondrial volume. These results provide molecular evidence for wide-scale remodeling in AK1-deficient muscles aimed at preservation of efficient energetic communication between ATP producing and utilizing cellular sites.
AB - Genetic ablation of adenylate kinase 1 (AK1), a member of the AK family of phosphotransfer enzymes, disturbs muscle energetic economy and decreases tolerance to metabolic stress, despite rearrangements in alternative high energy phosphoryl transfer pathways. To define the mechanisms of this adaptive response, soleus and gastrocnemius muscles from AK1-/- mice were characterized by cDNA array profiling, Western blot and ultrastructural analysis. We demonstrate that AK1 deficiency induces fiber-type specific variation in groups of transcripts involved in glycolysis and mitochondrial metabolism and in gene products defining structural and myogenic events. This was associated with increased phosphotransfer capacities of the glycolytic enzymes pyruvate kinase and 3-phosphoglycerate kinase. Moreover, in AK1-/- mice, fast-twitch gastrocnemius, but not slow-twitch soleus, had an increase in adenine nucleotide translocator (ANT) and mitochondrial creatine kinase protein, along with a doubling of the intermyofibrillar mitochondrial volume. These results provide molecular evidence for wide-scale remodeling in AK1-deficient muscles aimed at preservation of efficient energetic communication between ATP producing and utilizing cellular sites.
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U2 - 10.1074/jbc.M211465200
DO - 10.1074/jbc.M211465200
M3 - Article
C2 - 12562761
AN - SCOPUS:0038644934
SN - 0021-9258
VL - 278
SP - 12937
EP - 12945
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 15
ER -