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Seitaj 2020 Cells

From Bioblast
Publications in the MiPMap
Seitaj B, Maull F, Zhang L, Wüllner V, Wolf C, Schippers P, La Rovere R, Distler U, Tenzer S, Parys JB, Bultynck G, Methner A (2020) Transmembrane BAX inhibitor-1 motif containing protein 5 (TMBIM5) sustains mitochondrial structure, shape, and function by impacting the mitochondrial protein synthesis machinery. Cells 9:E2147.

» PMID: 32977469 Open Access

Seitaj Bruno, Maull Felicia, Zhang Li, Wuellner Verena, Wolf Crhsitina, Schippers Philipp, La Rovere Rita, Distler Ute, Tenzer Stefan, Parys Jan B, Bultynck Geert, Methner Axel (2020) Cells

Abstract: The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates with the Parkinson's disease-associated protein CHCHD2 in the inner mitochondrial membrane. We here used CRISPR-Cas9-mediated knockout HAP1 cells to shed further light on the function of TMBIM5 in physiology and cell death susceptibility. We found that compared to wild type, TMBIM5-knockout cells were smaller and had a slower proliferation rate. In these cells, mitochondria were more fragmented with a vacuolar cristae structure. In addition, the mitochondrial membrane potential was reduced and respiration was attenuated, leading to a reduced mitochondrial ATP generation. TMBIM5 did not associate with Mic10 and Mic60, which are proteins of the mitochondrial contact site and cristae organizing system (MICOS), nor did TMBIM5 knockout affect their expression levels. TMBIM5-knockout cells were more sensitive to apoptosis elicited by staurosporine and BH3 mimetic inhibitors of Bcl-2 and Bcl-XL. An unbiased proteomic comparison identified a dramatic downregulation of proteins involved in the mitochondrial protein synthesis machinery in TMBIM5-knockout cells. We conclude that TMBIM5 is important to maintain the mitochondrial structure and function possibly through the control of mitochondrial biogenesis. Keywords: TMBIM, Cell death, Cell survival, Mitochondria, Mitochondrial metabolism Bioblast editor: Plangger M O2k-Network Lab: DE Mainz Methner A

Labels: MiParea: Respiration, mt-Structure;fission;fusion, mt-Membrane, Genetic knockout;overexpression 

Stress:Cell death  Organism: Human  Tissue;cell: Kidney  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k