Rat liver mitochondrial proteome: Changes associated with aging and acetyl-L-carnitine treatment

Musicco, Clara; Capelli, Valentina; Pesce, Vito; Timperio, Anna Maria; Calvani, Menotti; Mosconi, Luigi; Cantatore, Palmiro; Gadaleta, Maria Nicola

doi:10.1016/j.jprot.2011.05.041

Cited by 29 publications

(19 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results suggest a far more complex mechanism of action for this metabolite, which is not consistent with an immediate, direct replenishment of myocardial carnitine levels. Precisely how ALCAR improves IFM CPT1 activity in aged rat hearts is not currently known; however, a significant body of evidence indicates that it facilitates a number of metabolic changes (Hagen et al, 1998a, 2002; Musicco et al, 2009, 2011; Pesce et al, 2010), which may ultimately improve CPT1 activity specifically in IFM. Even though ALCAR is not a classical free radical terminating molecule, nevertheless, it decreases the formation of nitro-tyrosine protein adducts in alcohol-induced brain damage (Rump et al, 2010), and limits oxidative damage in the heart following ischemia/reperfusion injury (Calvani et al, 2000; Cui et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart

Gómez

Heath

Hagen

2012

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24–28 mos) Fischer 344 rats were fed ± acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p < 0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p < 0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished Vmax and Km (60% and 49% respectively, p < 0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

show abstract

Section: Discussionmentioning

confidence: 99%

Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart

Gómez

Heath

Hagen

2012

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

show abstract

“…Another study also investigated mitochondrial liver proteome in male Fischer 344 Charles-River rats between 12 and 28 months of age using 2-D PAGE combined with ESI-MS (Musicco et al, 2011). Here proteins involved in metabolism (TCA, fatty acid ␤-oxidation, urea cycle), OXPHOS (complex I and ATP synthase), sulphur metabolism (rhodanese), and redox homeostasis (peroxiredoxin 3, glutathione peroxidase 1) were shown to be altered in older animals.…”

Section: Livermentioning

confidence: 99%

Proteome analysis in the assessment of ageing

Nkuipou‐Kenfack

Koeck

Mischak

et al. 2014

Ageing Research Reviews

View full text Add to dashboard Cite

“…Among the proteins with altered amounts, 23 were decreased and eight increased in abundance. Interestingly, in a recent study on rat liver mitochondrial acetylome, it has been shown that in vivo treatment of elderly rats with acetylcarnitine altered the abundance of 26 proteins with 22 being decreased (Musicco et al, 2011; Pesce et al, 2012). In this latter study several proteins with decreased amount were identical to those found in the present study (marked by asterisks in Table 4).…”

Section: Resultsmentioning

confidence: 99%

Acetyl-l-carnitine increases mitochondrial protein acetylation in the aged rat heart

Kerner

Yohannes

Lee

et al. 2015

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

Previously we showed that in vivo treatment of elderly Fisher 344 rats with acetylcarnitine abolished the age-associated defect in respiratory chain complex III in interfibrillar mitochondria and improved the functional recovery of the ischemic/reperfused heart. Herein we explored mitochondrial protein acetylation as a possible mechanism for acetylcarnitine’s effect. In vivo treatment of elderly rats with acetylcarnitine restored cardiac acetylcarnitine content and increased mitochondrial protein lysine acetylation and increased the number of lysine-acetylated proteins in cardiac subsarcolemmal and interfibrillar mitochondria. Enzymes of the tricarboxylic acid cycle, mitochondrial β-oxidation, and ATP synthase of the respiratory chain showed the greatest acetylation. Acetylation of isocitrate dehydrogenase, long-chain acyl-CoA dehydrogenase, complex V, and aspartate aminotransferase was accompanied by decreased catalytic activity. Several proteins were found to be acetylated only after treatment with acetylcarnitine, suggesting that exogenous acetylcarnitine served as the acetyl-donor. 2-D fluorescence difference gel electrophoresis analysis revealed that acetylcarnitine treatment also induced changes in mitochondrial protein amount; a twofold or greater increase/decrease in abundance was observed for thirty one proteins. Collectively, our data provide evidence for the first time that in the aged rat heart in vivo administration of acetylcarnitine provides acetyl groups for protein acetylation and affects the amount of mitochondrial proteins.

show abstract

Rat liver mitochondrial proteome: Changes associated with aging and acetyl-L-carnitine treatment

Cited by 29 publications

References 75 publications

Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart

Acetyl-l-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the l-carnitine content in the rat heart

Proteome analysis in the assessment of ageing

Acetyl-l-carnitine increases mitochondrial protein acetylation in the aged rat heart

Contact Info

Product

Resources

About