A star is born: TBMIM5 as a novel Ca2+ channel at the inner mitochondrial membrane

Calcium transfer between the endoplasmic reticulum, theh major intracellular calcium-storage organelle, and the mitochondria critally control cell survival and death process in health and disease (Krols M, Bultynck G, janssens A, J cell Biol, 2016). This process is modulated by several proto-oncogenes and tumor suppressors (Bittermieux M, Parys JP, Pinton P, Bultynck G, BBA-Mol Cell Res, 2016).In this project we aim to investigate novel molecular players in this process. In collaboration with Dr. Axel Methner, we found that TMBIM5, a protein related to Bax Inhibitor-1, previously identified as an ER calcium-leak channel (Bultynck G et al, J Biol Chem, 2012; Bultynck G et al, Sci Signal, 2014), is located at the mitochondria. We will assess whether TMBIM5 is a novel mitochondrial calcium-uptake system. We therefore developed TMBIM5-deficient HAP1 cells re-expressing wild-type and mutant TMBIM5. These cells will be analysed for their mitochondrial calcium responses using chemical and genetically encoded calcium dyes. Mitochondrial physiology including oxygen consumption rate and sensitivity to mitochondrial stress using rotenone will be examined.In a second part of the project we will focus on the regulation of VDAC1-mediated calcium uptake by Bcl-2/Bcl-xL proteins. We previously focussed on the BH$-domain biology (Monaco G et al, J Biol Chem, 2015), but now aim to focus on the full length Bcl-2/Bcl-xL proteins.

Jaar van publicatie:2021

Toegankelijkheid:Open