Contribution of Yeast Studies to the Understanding of BCL-2 Family Intracellular Trafficking

• Published in: International journal of molecular sciences Vol. 22; no. 8; p. 4086
• Main Authors: Rouchidane Eyitayo, Akandé, Gonin, Mathilde, Arokium, Hubert, Manon, Stéphen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15.04.2021; MDPI
• Subjects: Animals; Apoptosis; Autophagy; Bcl-2 family; Bcl-2 protein; Cell death; Compartments; Cytosol; Ectopic expression; Endoplasmic reticulum; Homology; Humans; Intracellular; Intracellular Space - metabolism; Life Sciences; Localization; Mammals; Mitochondria; Mitochondria-Associated Membranes; Models, Biological; Molecular modelling; Oxidative stress; Permeability; Phosphorylation; Protein Transport; Proteins; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Regulation; Review; Saccharomyces cerevisiae - metabolism; Translocase of Outer Membrane; Yeast; Mitochondria-Associated Membranes; apoptosis; mitochondria; Translocase of Outer Membrane; endoplasmic reticulum; Bcl-2 family
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22084086

BCL-2 family members are major regulators of apoptotic cell death in mammals. They form an intricate regulatory network that ultimately regulates the release of apoptogenic factors from mitochondria to the cytosol. The ectopic expression of mammalian BCL-2 family members in the yeast which lacks BCL-2 homologs, has been long established as a useful addition to the available models to study their function and regulation. In yeast, individual proteins can be studied independently from the whole interaction network, thus providing insight into the molecular mechanisms underlying their function in a living context. Furthermore, one can take advantage of the powerful tools available in yeast to probe intracellular trafficking processes such as mitochondrial sorting and interactions/exchanges between mitochondria and other compartments, such as the endoplasmic reticulum that are largely conserved between yeast and mammals. Yeast molecular genetics thus allows the investigation of the role of these processes on the dynamic equilibrium of BCL-2 family members between mitochondria and extramitochondrial compartments. Here we propose a model of dynamic regulation of BCL-2 family member localization, based on available evidence from ectopic expression in yeast.