Muntane Jordi

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COST Action CA15203 (2016-2021): MitoEAGLE
Evolution-Age-Gender-Lifestyle-Environment: mitochondrial fitness mapping

Muntane Jordi

MitoPedia topics: MitoPedia topic::EAGLE

COST: Has COST::Member

COST WG3: Has COST WG3::WG3 COST WG4: Has COST WG4::WG4

Name	Has lastname::Muntane Has firstname::Jordi, Has title::Dr.
Institution	[[Has institution::::::::::::::::: Co-Head “Oncology Surgery, Cell Therapy and Transplant Organs” group (Laboratory 209) InstitutodeBiomedicinadeSevilla-IBiS Campus del Hospital Universitario Virgen del Rocío]]
Address	Has address::Avenida Manuel Siurot s/n, Has area code::41013
City	In city::Sevilla
State/Province	In state::
Country	In country::Spain
Email	Has mailaddress::[email protected]
Weblink	Weblink::
O2k-Network Lab	{{#ask:has member::Muntane Jordi}}

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MitoEAGLE Short-Term Scientific Mission

- - - STSM Grant Period 2

Work Plan summary

1. Aim & motivation - Please explain the scientific and/or other motivation for the STSM and what scientific and/or other outcomes you aim to accomplish with the STSM.

2. Proposed contribution to the scientific objectives of the Action.

3. Techniques - Please detail what techniques or equipment you may learn to use, if applicable.

4. Planning - Please detail the steps you will take to achieve your proposed aim.

MOTIVATION AND WORK PLAN STUDY Aim and motivation Our group investigates the intracellular signaling leading to the induction of cell death by Sorafenib in liver cancer cells. Sorafenib is the ecommended treatment in patients with advanced liver cancer. We have showed that the induction of apoptosis by Sorafenib is associated with induction of endoplasmic reticulum stress, autophagy and apoptosis in HepG2 cells. Interestingly, the antitumoral properties of Sorafenib is related to potent antioxidant properties and downregulation of Nrf2 signaling. However, we have also observed that Sorafenib induces mitochondrial hyperpolarization which suggest an alteration of mitochondrial function, as well as potential risk of ROS production and release of proapoptotic factors. In fact, mitochondria play a relevant role in the unfolded protein response (Qureshi et al. The mitochondrial unfolded protein response: signaling from the powerhouse. J Biol Chem 2017;292(33):13500â€“13506) and apoptosis (Kurose et al. Cancer Res 2009;69(9):3927-3936). In addition, it has been observed that Sorafenib impaired mitochondrial function in rat heart isolated mitochondria (Will et al. Toxicol Sci 2009:106(1); 153-161). All this ackground suggests that mitochondrial disturbances plays a role during the induction of cell death in Sorafenib-treated HepG2 cells. The scientific interest of the SMTS is the elucidation of the alteration of mitochondrial function and its potential relation with the induction of cell death by Sorafenib in HepG2 cells. The outcomes to be accomplished during the SMTS in the lab of Prof. Zuzana Cervinkova (Department of Physiology, Faculty of Medicine, Hradec Kralove, Czech Republic) is to determine in permeabilized HepG2 cells:

1)Effect of Sorafenib on the ETS capacity in living cells in HepG2 cells

2)Evaluate the participation of complex I- and II-, fatty acids and malate- and dihydroxy acetone phosphate-related ETS capacity using different substrates and inhibitors.

3)Mitochondrial ROS production

4)Measurement of Residual Oxygen Consumption (ROX) using complex I complex II and complex III inhibitors Proposed Contributions to the Scientific Objectives of the Action The overall objective of the MitoEAGLE network is to improve our knowledge on mitochondrial function in health and disease related to Evolution, Age, Gender, Lifestyle and Environment.

In particular, I have recently incorporated to the COST Action CA15203 MitoEAGLE in the “TG3.2 Liver” and “TG4.2 Cultured cells” working groups. This WGs are focused in the characterization of mitochondrial function of stablished cell lines, among them primary and liver cancer cells in control and physiopathological conditions. I believe that the objectives of the SMTS are perfectly in concordance with those of the Action and WGs. Techniques and Equipment to be used The in vitro experiments will be based in permeabilized HepG2 cells. The maintenance of HepG2 cells requires the use of cell culture room fully equipped. Sorafenib will be administered to cell culture and/or in permeabilized cells in suspension at therapeutic dose (10 μM). The different measurements will be carried out using O2k-FluoRespirometer (Oroboros Instruments). Planning and steps to achieve The experiments can be perfectly done during the scheduled SMTS period (November 15-December 1). 1st phase: 15-20 November Culture, maintenance and expansion of culture of HepG2 cells. 2nd phase: 20-25 November

1)Effect of Sorafenib on the ETS capacity in living cells in HepG2 cells

2)Evaluate the participation of complex I- and II-, fatty acids and malate- and dihydroxy acetone phosphate-related ETS capacity using different substrates and inhibitors.

3)Evaluation of data 3rd phase: 27-30 November 1)Mitochondrial ROS production

2)Measurement of Residual Oxygen Consumption (ROX) using complex I complex II and complex III inhibitors

3)Evaluation of data and conclusions of the SMTS

Participated at

MitoEAGLE

Dr. Muntané will work in two specific areas: 1) Lipotoxicity-related cell mechanism in primary cultured human hepatocytes, and Sorafenib-induced insulin resistance in hepatocellular carcinoma cell lines; and 2) The alteration of different intracellular signaling induced by Sorafenib and immunosuppressants in liver cancer cells. Working groups: TG3.2 Liver and TG4.2 Cultured cells. - Muntane Jordi (2017).