Transmembrane BAX Inhibitor-1 Motif Containing Protein 5 (TMBIM5) Sustains Mitochondrial Structure, Shape, and

Bruno Seitaj1, Felicia Maull2, Li Zhang2

  • 1KU Leuven, Laboratory of Molecular and Cellular Signaling, Department of Cellular and Molecular Medicine and Leuven Kanker Instituut (LKI), Campus Gasthuisberg ON-I Bus 802, 3000 Leuven, Belgium.

Cells
|September 26, 2020
PubMed

Insights

Transmembrane Bax Inhibitor-1 motif (TMBIM) protein 5 (TMBIM5) is crucial for mitochondrial structure and function. Knocking out TMBIM5 impairs cell growth, mitochondrial integrity, and increases apoptosis sensitivity.

Area of Science:

  • Cell Biology
  • Mitochondrial Biology
  • Apoptosis Research

Background:

  • The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is involved in cell death.
  • TMBIM5 is the sole mitochondrial member, influencing cristae organization and interacting with CHCHD2.

Purpose of the Study:

  • To investigate the physiological role and cell death susceptibility of TMBIM5 using CRISPR-Cas9 knockout HAP1 cells.

Main Methods:

  • CRISPR-Cas9 gene editing to create TMBIM5 knockout HAP1 cells.
  • Analysis of cell morphology, proliferation, mitochondrial structure, membrane potential, respiration, and ATP generation.
  • Proteomic analysis to identify protein expression changes.

Main Results:

  • TMBIM5 knockout cells exhibited smaller size, slower proliferation, fragmented mitochondria with vacuolar cristae, reduced mitochondrial membrane potential, and attenuated respiration.
  • Knockout cells showed increased sensitivity to apoptosis-inducing agents.
  • Proteomics revealed downregulation of mitochondrial protein synthesis machinery in TMBIM5-knockout cells.

Conclusions:

  • TMBIM5 is essential for maintaining mitochondrial structure and function.
  • TMBIM5 may regulate mitochondrial biogenesis, impacting cell physiology and apoptosis susceptibility.

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