Pereira da Silva Grilo da Silva Filomena

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

Pereira da Silva Grilo da Silva Filomena

MitoPedia topics: EAGLE

COST: Member

COST WG4: WG4

COST ECI: ECI

Name	Pereira da Silva Grilo da Silva Filomena, PhD.
Institution	Center for Neuroscience and Cell Biology, University of Coimbra, PT Visiting scientist Understanding mitochondrial remodeling in NAFLD Filomena Pereira da Silva Grilo da Silva is a visiting scientist at Oroboros Instruments within the Secondment MtFOIE GRAS from October 2017 to February 2018 and in March 2019.
Address	Biocant Park, 3060-197
City	Catanhede
State/Province
Country	Portugal
Email	[email protected]
Weblink
O2k-Network Lab

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Publications

	Published	Reference
BEC 2020.1 doi10.26124bec2020-0001.v1	2020	Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. https://doi.org/10.26124/bec:2020-0001.v1

Abstracts

	Published	Reference
Komlodi 2023 EUROMIT2023 Bologna	2023	Komlódi T, Silva FSG, Duarte AI, Mena D, Garcia-Souza LF, Makrecka-Kuka M, Bento G, Grilo LF, Oliveira PJ, Gnaiger E (2023) Off-target effects of etomoxir: inhibition of mitochondrial Complex I and fatty acid oxidation. EUROMIT2023 International Conference on Mitochondrial Pathology.
Silva 2019 MiPschool Coimbra	2019	Off-target effects of etomoxir on mitochondrial Complex I.
Silva 2019 ESCI2019	2019	Silva FSG, Komlodi T, Garcia-Souza LF, Bento G, Doerrier C, Oliveira PJ, Gnaiger E (2019) Can fatty acid oxidation be specifically blocked by the CPT1 inhibitor etomoxir?
Pereira da Silva Grilo da Silva 2018 MiP2018	2018	The unspecific effect of etomoxir on mitochondrial respiration.
Silva 2017 MiP2017	2017	No abstract.

MitoEAGLE Inclusiveness Target Countries - Conference Grant

- - - Conference Grant Grand Period 3

Scientific report - ESCI2018

MitoEAGLE Short-Term Scientific Mission

- - - STSM Grant Period 3

Work Plan summary

1. The liver mitochondrial dysfunction plays an important role in the progression of non-alcoholic steatohepatitis, therefore improved protocols are required to evaluate mitochondrial fitness in the course of disease. Etomoxir is a well-known compound which irreversibly inhibits the carnitine palmitoyltransferase (CPT-1) in the outer surface of the mitochondrial inner membrane, therefore, blocks the transport of fatty acids into the mitochondrial matrix for further oxidation. However, among others we have shed light on the unspecific effect of etomoxir on the mitochondrial fatty acid oxidation (FAO; F-pathway linked respiration) in permeabilized Huh7 liver cells and mitochondria isolated from mouse liver. In our previous study (data not published) we have observed that the effect of etomoxir is concentration dependent. Low concentration (~40 µM) of etomoxir might inhibit NADH-linked respiration supported by glutamate or pyruvate plus malate. We have seen that high concentration of etomoxir (~200 µM) might block not only the NADH-linked pathway but also the Succinate-linked respiration.

The aim of the secondment is to adjust the optimal etomoxir concentration which does not exert inhibitory effect towards other respiratory pathways and specifically blocks FAO on mitochondria.

2. The goal of this secondment is to provide standardized protocols to study FAO and to deepen our knowledge about the effect of etomoxir on F-pathway linked mitochondrial respiration and get rid of the artefacts created by overdosage of the inhibitor.

Oroboros laboratory would provide a platform with its instrumental background, with its protocols, its experience and its international team to the objectives and aim of MitoEAGLE.

3. High-resolution Respirometry experiments will be performed on isolated mitochondria from mouse liver, heart and brain as well as permeabilized Huh7 liver cell lines. In order to detect FAO, we have used palmitoylcarnitine as source of fatty acid, which needs CPT-1 to enter the mitochondrial matrix and low concentration of malate supporting FAO. We also want to test other sources of fatty acid such as palmitoyl-CoA + carnitine + low amount of malate or palmitate + CoA + carnitine, which might influence the effect of etomoxir on CPT-1.

Participated at

Visiting scientist in the Oroboros O2k-Laboratory

Filomena Pereira da Silva Grilo da Silva: Visiting scientist at the Oroboros O2k-Laboratory

March 04 to March 22 2019
October 01 2016 to February 28 2017