Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging.
Mitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in ske...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3720551?pdf=render |
| _version_ | 1819031055167913984 |
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| author | Anna-Maria Joseph Peter J Adhihetty Nicholas R Wawrzyniak Stephanie E Wohlgemuth Anna Picca Gregory C Kujoth Tomas A Prolla Christiaan Leeuwenburgh |
| author_facet | Anna-Maria Joseph Peter J Adhihetty Nicholas R Wawrzyniak Stephanie E Wohlgemuth Anna Picca Gregory C Kujoth Tomas A Prolla Christiaan Leeuwenburgh |
| author_sort | Anna-Maria Joseph |
| collection | DOAJ |
| description | Mitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in skeletal muscle from animals (young; 3-6 months and older; 8-15 months) expressing a proofreading-deficient version of mtDNA polymerase gamma (PolG). This progeroid aging model exhibits elevated mtDNA mutation rates, mitochondrial dysfunction, and a premature aging phenotype that includes sarcopenia. We found increased expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its target proteins, nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam) in PolG animals compared to wild-type (WT) (P<0.05). Muscle from older PolG animals displayed higher mitochondrial fission protein 1 (Fis1) concurrent with greater induction of autophagy, as indicated by changes in Atg5 and p62 protein content (P<0.05). Additionally, levels of the Tom22 import protein were higher in PolG animals when compared to WT (P<0.05). In contrast, muscle from normally-aged animals exhibited a distinctly different expression profile compared to PolG animals. Older WT animals appeared to have higher fusion (greater Mfn1/Mfn2, and lower Fis1) and lower autophagy (Beclin-1 and p62) compared to young WT suggesting that autophagy is impaired in aging muscle. In conclusion, muscle from mtDNA mutator mice display higher mitochondrial fission and autophagy levels that likely contribute to the sarcopenic phenotype observed in premature aging and this differs from the response observed in normally-aged muscle. |
| first_indexed | 2024-12-21T06:39:58Z |
| format | Article |
| id | doaj.art-cd8ba1f6513944c9aaafa649cfe05d97 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T06:39:58Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cd8ba1f6513944c9aaafa649cfe05d972022-12-21T19:12:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6932710.1371/journal.pone.0069327Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging.Anna-Maria JosephPeter J AdhihettyNicholas R WawrzyniakStephanie E WohlgemuthAnna PiccaGregory C KujothTomas A ProllaChristiaan LeeuwenburghMitochondrial DNA (mtDNA) mutations lead to decrements in mitochondrial function and accelerated rates of these mutations has been linked to skeletal muscle loss (sarcopenia). The purpose of this study was to investigate the effect of mtDNA mutations on mitochondrial quality control processes in skeletal muscle from animals (young; 3-6 months and older; 8-15 months) expressing a proofreading-deficient version of mtDNA polymerase gamma (PolG). This progeroid aging model exhibits elevated mtDNA mutation rates, mitochondrial dysfunction, and a premature aging phenotype that includes sarcopenia. We found increased expression of the mitochondrial biogenesis regulator peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and its target proteins, nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam) in PolG animals compared to wild-type (WT) (P<0.05). Muscle from older PolG animals displayed higher mitochondrial fission protein 1 (Fis1) concurrent with greater induction of autophagy, as indicated by changes in Atg5 and p62 protein content (P<0.05). Additionally, levels of the Tom22 import protein were higher in PolG animals when compared to WT (P<0.05). In contrast, muscle from normally-aged animals exhibited a distinctly different expression profile compared to PolG animals. Older WT animals appeared to have higher fusion (greater Mfn1/Mfn2, and lower Fis1) and lower autophagy (Beclin-1 and p62) compared to young WT suggesting that autophagy is impaired in aging muscle. In conclusion, muscle from mtDNA mutator mice display higher mitochondrial fission and autophagy levels that likely contribute to the sarcopenic phenotype observed in premature aging and this differs from the response observed in normally-aged muscle.http://europepmc.org/articles/PMC3720551?pdf=render |
| spellingShingle | Anna-Maria Joseph Peter J Adhihetty Nicholas R Wawrzyniak Stephanie E Wohlgemuth Anna Picca Gregory C Kujoth Tomas A Prolla Christiaan Leeuwenburgh Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. PLoS ONE |
| title | Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. |
| title_full | Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. |
| title_fullStr | Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. |
| title_full_unstemmed | Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. |
| title_short | Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. |
| title_sort | dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging |
| url | http://europepmc.org/articles/PMC3720551?pdf=render |
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