bims-tricox 2023-11-19 papers

Issue of 2023–11–19
three papers selected by
Yash Verma, University of Zurich

Cell Mol Life Sci. 2023 Nov 16. 80(12): 361

GTPBP8 is required for mitoribosomal biogenesis and mitochondrial translation.

Liang Wang, Taru Hilander, Xiaonan Liu, Hoi Ying Tsang, Ove Eriksson, Christopher B Jackson, Markku Varjosalo, Hongxia Zhao.

Mitochondrial translation occurs on the mitochondrial ribosome, also known as the mitoribosome. The assembly of mitoribosomes is a highly coordinated process. During mitoribosome biogenesis, various assembly factors transiently associate with the nascent ribosome, facilitating the accurate and efficient construction of the mitoribosome. However, the specific factors involved in the assembly process, the precise mechanisms, and the cellular compartments involved in this vital process are not yet fully understood. In this study, we discovered a crucial role for GTP-binding protein 8 (GTPBP8) in the assembly of the mitoribosomal large subunit (mt-LSU) and mitochondrial translation. GTPBP8 is identified as a novel GTPase located in the matrix and peripherally bound to the inner mitochondrial membrane. Importantly, GTPBP8 is specifically associated with the mt-LSU during its assembly. Depletion of GTPBP8 leads to an abnormal accumulation of mt-LSU, indicating that GTPBP8 is critical for proper mt-LSU assembly. Furthermore, the absence of GTPBP8 results in reduced levels of fully assembled 55S monosomes. This impaired assembly leads to compromised mitochondrial translation and, consequently, impaired mitochondrial function. The identification of GTPBP8 as an important player in these processes provides new insights into the molecular mechanisms underlying mitochondrial protein synthesis and its regulation.

Keywords: GTP binding protein; Mitochondria; Mitochondrial translation; Mitoribosomal protein; Mitoribosome; Mitoribosome assembly; Mitoribosome large subunit

DOI: https://doi.org/10.1007/s00018-023-05014-0

Biochim Biophys Acta Mol Cell Res. 2023 Jul 04. pii: S0167-4889(23)00101-5. [Epub ahead of print] 119529

Mitochondrial entry gate as regulatory hub.

Fabian den Brave, Nikolaus Pfanner, Thomas Becker.

Mitochondria import 1000-1300 different precursor proteins from the cytosol. The main mitochondrial entry gate is formed by the translocase of the outer membrane (TOM complex). Molecular coupling and modification of TOM subunits control and modulate protein import in response to cellular signaling. The TOM complex functions as regulatory hub to integrate mitochondrial protein biogenesis and quality control into the cellular proteostasis network.

Keywords: Mitochondria; Protein sorting; Proteostasis; Quality control; Stress response; TOM complex

DOI: https://doi.org/10.1016/j.bbamcr.2023.119529

STAR Protoc. 2023 Nov 15. pii: S2666-1667(23)00572-5. [Epub ahead of print]4(4): 102605

Protocol to study human mitochondrial ribosome using quantitative density gradient analysis by mass spectrometry and complexome profiling analysis.

Petra Páleníková, Michal Minczuk, Pedro Rebelo-Guiomar.

Dynamic macromolecular complexes containing a large number of components are often difficult to study using conventional approaches, such as immunoblotting. Here, we present a protocol for the analysis of macromolecular complexes in near-native conditions using a flexible setup to suit different cellular targets. We describe analysis of human mitochondrial ribosome, composed of 82 proteins, in a standardized way using density gradient ultracentrifugation coupled to quantitative mass spectrometry and subsequent analysis of the generated data (ComPrAn). For complete details on the use and execution of this protocol, please refer to Páleníková et al.1 and Rebelo-Guiomar et al.2.

Keywords: Bioinformatics; Protein Expression and Purification; Proteomics

DOI: https://doi.org/10.1016/j.xpro.2023.102605