Jaskiewicz A

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MiPsociety
COST Action CA15203 MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping


 

Jaskiewicz A


MitoPedia topics: EAGLE 

COST: Member COST WG1: WG1


Name Jaskiewicz Anna,
Institution SGGW - Warsaw University of Life Sciences, PL
Address Nowoursynowska 166, 02-787
City Warszawa
State/Province
Country Poland
Email ancpatrin@gmail.com
Weblink
O2k-Network Lab


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Publications

 PublishedReference
Jaskiewicz 2019 J Clin Med2019Jaśkiewicz A, Pająk B, Łabieniec-Watała M, De Palma C, Orzechowski A (2019) Diverse action of selected statins on skeletal muscle cells - An attempt to explain the protective effect of geranylgeraniol (GGOH) in statin-associated myopathy (SAM). J Clin Med 8:694.
Gnaiger 2019 MitoFit Preprint Arch2019Gnaiger E, Aasander Frostner E, Abdul Karim N, Abdel-Rahman EA, Abumrad NA, Acuna-Castroviejo D, Adiele RC, et al (2019) Mitochondrial respiratory states and rates. MitoFit Preprint Arch doi:10.26124/mitofit:190001.v5.

Abstracts

 PublishedReference
Jaskiewicz 2018 MiPschool Tromso2018
MiPsociety
No abstract.

MitoEAGLE Short-Term Scientific Mission

Work Plan summary
Recent research in our laboratory is dedicated to the molecular mechanism of statin mytotoxicity with special reference to autophagy. Statins, 3-hydroxy-3-methylglutaryl coenzym A (HMG-CoA) reductase inhibitors are in turn antihyperlipidemic and highly successful in decreasing the intracellular synthesis of cholesterol as cholesterol lowering drugs. The use of statins is very often associated with muscle atrophy. In our research we use atorvastatin, simvastatin and also in contrast to statins MβCD- cholesterol chelator which makes membranes poorer in nanodomains (lipid rafts- whose main component is cholesterol). We use C2C12 mouse skeletal muscle satelite cells to monitor myogenesis. Our scientific reports indicate that Rap1 protein not Rheb as previously thought is responsible for activation of mTORC1. mTORC1 provides the basis for pathways responsible for cellular protein synthesis, primarily cell growth and viability. We have found that under conditions of inhibition of synthesis of intermediates of mevalonate pathway only geranylgeranyl transferase determines the survival of myocytes during myogenesis. Very important aspect of our research is autophagy. We have done cytofluorescence analysis of the autophagy intensity index and estimated the expression level of specific markers of autophagy- Beclin 1 and MAP LC3I/II during myogenesis under conditions of inhibition of mevalonic acid metabolism. We can safely say that cytoprotective autophagy is elevated in myocytes during myogenesis. Statins reduce the level of autophagy during myogenesis and this effect can be reversed by geranylgeraniol. The next step of our research will be to determine what is the basis of the cytoprotective effect of geranylgeraniol. Our research shows that geranylgeraniol through protein prenylation may be responsible for cytoprotective autophagy. Following the results of J. Sin et all. (2016) the type of autophagy dominant in differentiation of muscle cells is mitophagy. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. This phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. That is why I want to pay higher attention on mitophagy and changes in mitochondrial network during muscle cell differentiation under conditions of inhibition of mevalonic acid metabolism. The aim of our study is to discover the link between the inhibition of autophagy during muscle cells differentiation by statins and the pathway on which geranylgeraniol increases cells survival. To manage the energy requirements of the mature muscular tissue mitochondrial metabolism must be primarily focused on oxygen processes. Based on our research and the cytoprotective effect of geranylgeraniol, we would like to investigate whether geranylgeraniol also affects the alteration of metabolic profile of mitochondria during muscle cell differentiation. Co-operation with one of the MitoEAGLE host institution- University Hospital “Luigi Sacco” will be helpful for us to investigate the alterations in the mitochondrial network. The main aim of this internship will be comparison between the mitochondrial metabolism by mitochondrial respirometry at various stages of muscle cells differentiation under conditions of reversible inhibition of mevalonic acid metabolism. During Short - Term Scientific Mission MitoEAGLE I would like also investigate mitochondrial network remodeling using confocal microscopy during differentiation of C2C12 cells. The molecular mechanism of myotoxicity of statins is a matter of debate. Statins are the most commonly used prescription drugs in the World. Very common side effects reported in patients taking statins are muscle injuries such as myalgia, myositis and life threatening rhabdomyolysis. We found out that geranylgeraniol is able to restore the cytoprotective autophagy inhibited by statins. We assume that mitophagy inhibition is the most important point. Therefore, the identification of changes in the mitochondrial metabolic profile during muscle cells differentiation may be a missing element of this puzzle.

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