Muscle PGC-1α modulates hepatic mitophagy regulation during aging
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Muscle PGC-1α modulates hepatic mitophagy regulation during aging. / Christensen, Natascha Masselkhi; Ringholm, Stine; Buch, Bjørg Thiellesen; Gudiksen, Anders; Halling, Jens Frey; Pilegaard, Henriette.
In: Experimental Gerontology, Vol. 172, 112046, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Muscle PGC-1α modulates hepatic mitophagy regulation during aging
AU - Christensen, Natascha Masselkhi
AU - Ringholm, Stine
AU - Buch, Bjørg Thiellesen
AU - Gudiksen, Anders
AU - Halling, Jens Frey
AU - Pilegaard, Henriette
N1 - Publisher Copyright: © 2022
PY - 2023
Y1 - 2023
N2 - Aging has been suggested to be associated with changes in oxidative capacity, autophagy, and mitophagy in the liver, but a simultaneous evaluation of these key cellular processes is lacking. Moreover, skeletal muscle transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α has been reported to mediate inter-organ signaling through myokines with regulatory effects in the liver, but the potential role of muscle PGC-1α on hepatic changes with age remains to be resolved. The aim of the present study was therefore to investigate 1) the effect of aging on mitochondrial autophagy and mitophagy capacity in mouse liver and 2) whether muscle PGC-1α is required for maintaining autophagy and mitophagy capacity in the liver during aging. The liver was obtained from young (Young) and aged (Aged) inducible muscle-specific PGC-1α knockout (iMKO) and floxed littermate control mice (Lox). Aging increased liver p62, Parkin and BCL2/adenovirus E1B 19 kDa protein-interacting protein (BNIP)3 protein with no effect of muscle specific PGC-1α knockout, while liver Microtubule-associated protein 1A/1B-light chain 3(LC3) II/I was unchanged with age, but tended to be lower in iMKO mice than in controls. Markers of liver mitochondrial oxidative capacity and oxidative stress were unchanged with age and iMKO. However, Parkin protein levels in isolated liver mitochondria were 2-fold higher in Aged iMKO mice than in Aged controls. In conclusion, aging had no effect on oxidative capacity and lipid peroxidation in the liver. However, aging was associated with increased levels of autophagy and mitophagy markers. Moreover, muscle PGC-1α appears to regulate hepatic mitochondrial translocation of Parkin in aged mice, suggesting that the metabolic capacity of skeletal muscle can modulate mitophagy regulation in the liver during aging.
AB - Aging has been suggested to be associated with changes in oxidative capacity, autophagy, and mitophagy in the liver, but a simultaneous evaluation of these key cellular processes is lacking. Moreover, skeletal muscle transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α has been reported to mediate inter-organ signaling through myokines with regulatory effects in the liver, but the potential role of muscle PGC-1α on hepatic changes with age remains to be resolved. The aim of the present study was therefore to investigate 1) the effect of aging on mitochondrial autophagy and mitophagy capacity in mouse liver and 2) whether muscle PGC-1α is required for maintaining autophagy and mitophagy capacity in the liver during aging. The liver was obtained from young (Young) and aged (Aged) inducible muscle-specific PGC-1α knockout (iMKO) and floxed littermate control mice (Lox). Aging increased liver p62, Parkin and BCL2/adenovirus E1B 19 kDa protein-interacting protein (BNIP)3 protein with no effect of muscle specific PGC-1α knockout, while liver Microtubule-associated protein 1A/1B-light chain 3(LC3) II/I was unchanged with age, but tended to be lower in iMKO mice than in controls. Markers of liver mitochondrial oxidative capacity and oxidative stress were unchanged with age and iMKO. However, Parkin protein levels in isolated liver mitochondria were 2-fold higher in Aged iMKO mice than in Aged controls. In conclusion, aging had no effect on oxidative capacity and lipid peroxidation in the liver. However, aging was associated with increased levels of autophagy and mitophagy markers. Moreover, muscle PGC-1α appears to regulate hepatic mitochondrial translocation of Parkin in aged mice, suggesting that the metabolic capacity of skeletal muscle can modulate mitophagy regulation in the liver during aging.
KW - Aging
KW - Autophagy
KW - Liver
KW - Metabolism
KW - Parkin
KW - PGC-1α
U2 - 10.1016/j.exger.2022.112046
DO - 10.1016/j.exger.2022.112046
M3 - Journal article
C2 - 36521568
AN - SCOPUS:85144771594
VL - 172
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
M1 - 112046
ER -
ID: 331320340