A systems biological analysis links ROS metabolism to mitochondrial protein quality control

Kowald, Axel; Hamann, Andréa; Zintel, Sandra; Ullrich, Sebastian; Klipp, Edda; Osiewacz, Heinz D.

doi:10.1016/j.mad.2012.03.008

Cited by 30 publications

(30 citation statements)

References 47 publications

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“…Oxidative damage to polyunsaturated fatty acids of membrane lipids generates malondialdehyde (MDA) as one of the endproducts [14,15]. Studies on age-related changes in antioxidant defense system suggest that MnSOD is an essential front line defense against oxidative damage and its expression rate is important for cells to cope with ROS-mediated damage [11,16].…”

Section: Introductionmentioning

confidence: 99%

Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

Ademoğlu

Özcan²,

Tanrıkulu-Küçük³

et al. 2013

Turk J Bioch

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Objective: The aim of this study was to examine the age-and gender-related differences in peroxide production, manganese superoxide dismutase (MnSOD) activity and expression in liver mitochondria of Wistar rats at 12 and 24 months of age. Methods: The chemiluminometric method for peroxide production, fluorometric method for malondialdehyde (MDA) levels, cumene hydroperoxide assay for glutathione peroxidase (GPx), the nitroblue tetrazolium assay for MnSOD activity, and Western-blotting for MnSOD expression were used. Results: Mitochondrial peroxides are increased significantly in both genders as aging proceeded, and females exhibited more profound increment than the males. Mitochondrial SOD and GPx activities remained unaltered between 12 and 24 months of age, with no difference between two genders. The gender-and age-related differences were observed in MnSOD expression (p<0.01). The SOD activity per expressed enzyme protein was significantly decreased in 24-month-old animals of both genders (p<0.01). Female rats had a significantly lower ratio than their male counterparts (p<0.05). In females, the expression was not associated with the activity of MnSOD, while a positive correlation existed between these parameters in males (r=0.573, p=0.001). Enzyme expression was found to be significantly higher in female rats as compared to their male counterparts. Liver mitochondria are less prone to oxidative damage in female rats compared to males as observed at 12 and 24 months of age Conclusions: An involvement of factors other than estrogen seems to be relevant for the difference in the MnSOD activity and expression pattern between two genders. Key Words: oxidative stress, aging, gender differences, MnSOD, rat liver Conflict of interest: The authors declare that there is no conflict of interest. ÖZETAmaç: Çalışmamızda, 12 ve 24 aylık Wistar cinsi sıçanların karaciğer mitokondrilerinde yaş ve cinsiyet ile ilişkili olarak peroksit üretimi, mangan süperoksit dismutaz (MnSOD) aktivitesi ve ekspresyonundaki ortaya çıkan değişikliklerin incelenmesi amaçlanmıştır. Yöntemler: Peroksit üretimi kemilümünometrik, malondialdehit (MDA) düzeyi florometrik, glutatyon peroksidaz (GPx) kümen hidroperoksit, MnSOD aktivitesi nitroblue tetrazolium yöntemleri ile MnSOD ekspresyonu ise western blotting yöntemi ile ölçülmüştür. Bulgular: Her iki cinsiyette de yaş ilerledikçe SOD ve GPx aktivitelerinde anlamlı bir değişiklik oluşmadığı, mitokondriyal peroksit üretiminin ise anlamlı şekilde arttığı ve bu artışın dişi sıçanlarda daha belirgin olduğu saptanmıştır. MnSOD ekspresyonun da yaş ve cinsiyete bağlı olarak değişiklikler gösterdiği (p<0.01) ve eksprese edilen enzim proteini başına düşen enzim aktivitesinin 24 aylık sıçanlarda her iki cinsiyette de anlamlı olarak azalmakla birlikte (p<0.01) bu azalmanın dişi sıçanlarda erkek sıçanlara göre daha belirgin (p<0.05) olduğu görülmüştür. Erkek sıçanlarda MnSOD aktivitesi ile ekspresyonu arasında pozitif bir korelasyon (r=0.573, p=0.001) olduğu saptanmış, dişi sıçanlarda ise böyle bir il...

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Section: Introductionmentioning

confidence: 99%

Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

Ademoğlu

Özcan²,

Tanrıkulu-Küçük³

et al. 2013

Turk J Bioch

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“…A computational evaluation of data led to the proposal of a model in which the observed adverse phenotypic effects in PaSod3 overexpressors were explained to result from an increase in hydrogen peroxide levels due to elevated SOD-activity (Kowald et al, 2012). In order to validate this theoretical model and to generate additional data explaining the impact of hydrogen peroxide stress in more detail, we investigated PaSod3 overexpressors and the wild type further.…”

Section: Resultsmentioning

confidence: 99%

“…Since the abundance of the manganese binding PaSOD3 is approximately 80-fold higher in the PaSod3 overexpression strains than in the wild type (Kowald et al, 2012), we first analyzed the impact of this trace metal on growth of these strains. In order to provide optimal growth conditions, we grew strains on the widely used M2 semisynthetic medium.…”

Section: Supplementation Of Growth Medium With Manganese Leads To a Rmentioning

confidence: 99%

“…Strikingly, in Sod3 overexpressors, proteins of the mitochondrial quality control system including the hydrogen peroxide detoxification protein peroxiredoxin (PaPRX), the two proteases PaCLPP and PaLON and the general stress protein PaHSP60 exhibited an altered abundance and/or size. These data were used to generate a computational model that suggests an increase in cellular hydrogen peroxide levels in the PaSod3 overexpressors leading to oxidation of PaPRX and PaCLPP (Kowald et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide

Grimm

Osiewacz

2015

Experimental Gerontology

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“…The regulation of individual components of the ROS scavenging system is more complex and depending on the coordinated regulation of different components. Consequently the increase of just one component may not be beneficial but rather increase oxidative stress leading to adverse consequences [7,8]. In any case, if ROS scavenging systems become overwhelmed in their capacity, essential biomolecules such as nucleic acids, proteins or lipids can be damaged.…”

Section: Introductionmentioning

confidence: 99%

Quality control of mitochondria during aging: Is there a good and a bad side of mitochondrial dynamics?

2013

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Maintenance of functional mitochondria is essential in order to prevent degenerative processes leading to disease and aging. Mitochondrial dynamics plays a crucial role in ensuring mitochondrial quality but may also generate and spread molecular damage through a population of mitochondria. Computational simulations suggest that this dynamics is advantageous when mitochondria are not or only marginally damaged. In contrast, at a higher degree of damage, mitochondrial dynamics may be disadvantageous. Deceleration of fusion‐fission cycles could be one way to adapt to this situation and to delay a further decline in mitochondrial quality. However, this adaptive response makes the mitochondrial network more vulnerable to additional molecular damage. The “mitochondrial infectious damage adaptation” (MIDA) model explains a number of inconsistent and counterintuitive data such as the “clonal expansion” of mutant mitochondrial DNA. We propose that mitochondrial dynamics is a double‐edged sword and suggest ways to test this experimentally.

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A systems biological analysis links ROS metabolism to mitochondrial protein quality control

Cited by 30 publications

References 47 publications

Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

Age-related changes in the activity and expression of manganese superoxide dismutase, and mitochondrial oxidant generation in female and male rats

Manganese rescues adverse effects on lifespan and development in Podospora anserina challenged by excess hydrogen peroxide

Quality control of mitochondria during aging: Is there a good and a bad side of mitochondrial dynamics?

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