Kozieł 2011 J Invest Dermatol

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Kozieł R, Greussing R, Maier AB, Declercq L, Jansen-Dürr P (2011) Functional interplay between mitochondrial and proteasome activity in skin aging. J Invest Dermatol 131:594-603.

» PMID: 21191400 Open Access

Koziel R, Greussing R, Maier AB, Declercq L, Jansen-Duerr P (2011) J Invest Dermatol

Abstract: According to the mitochondrial theory of aging, reactive oxygen species (ROS) derived primarily from mitochondria cause cumulative oxidative damage to various cellular molecules and thereby contribute to the aging process. On the other hand, a pivotal role of the proteasome, as a main proteolytic system implicated in the degradation of oxidized proteins during aging, is suggested. In this study, we analyzed mitochondrial function in dermal fibroblasts derived from biopsies obtained from healthy young, middle-aged, and old donors. We also determined proteasome activity in these cells, using a degron-destabilized green fluorescent protein (GFP)-based reporter protein. We found a significant decrease in mitochondrial membrane potential in samples from aged donors, accompanied by a significant increase in ROS levels. Respiratory activity was not significantly altered with donor age, probably reflecting genetic variation. Proteasome activity was significantly decreased in fibroblasts from middle-aged donors compared with young donors; fibroblasts derived from the oldest donors displayed a high heterogeneity in this assay. We also found intraindividual coregulation of mitochondrial and proteasomal activities in all human fibroblast strains tested, suggesting that both systems are interdependent. Accordingly, pharmacological inhibition of the proteasome led to decreased mitochondrial function, whereas inhibition of mitochondrial function in turn reduced proteasome activity.


Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Jansen-Duerr P

Table: Respiratory control in human dermal fibroblasts
Source R/E (R-L)/E (E-L)/E Rox/E'
young 0.32 0.24 0.92 0.024
middle 0.30 0.23 0.93 0.025
old 0.34 0.25 0.90 0.030
A (46 years;9 PDL) 0.33 0.26 0.93 0.009
B (36 years;14 PDL) 0.29 0.26 0.97 0.012
C (29 years;18 PDL) 0.30 0.24 0.94 0.013

Cited by

Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.8.


Gnaiger E (2021) Bioenergetic cluster analysis – mitochondrial respiratory control in human fibroblasts. MitoFit Preprints 2021.8. - »Bioblast link«


Labels: MiParea: Respiration  Pathology: Aging;senescence  Stress:Oxidative stress;RONS  Organism: Human  Tissue;cell: Fibroblast  Preparation: Intact cells  Enzyme: Marker enzyme 

Coupling state: ROUTINE 

HRR: Oxygraph-2k 

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