bims-mitran 2023-03-05 papers

Issue of 2023–03–05
three papers selected by
Andreas Kohler, University of Graz

Trends Cell Biol. 2023 Feb 28. pii: S0962-8924(23)00020-X. [Epub ahead of print]

The multifaceted mitochondrial OXA insertase.

Bettina Homberg, Peter Rehling, Luis Daniel Cruz-Zaragoza.

Most mitochondrial proteins are synthesized in the cytosol and transported into mitochondria by protein translocases. Yet, mitochondria contain their own genome and gene expression system, which generates proteins that are inserted in the inner membrane by the oxidase assembly (OXA) insertase. OXA contributes to targeting proteins from both genetic origins. Recent data provides insights into how OXA cooperates with the mitochondrial ribosome during synthesis of mitochondrial-encoded proteins. A picture of OXA emerges in which it coordinates insertion of OXPHOS core subunits and their assembly into protein complexes but also participates in the biogenesis of select imported proteins. These functions position the OXA as a multifunctional protein insertase that facilitates protein transport, assembly, and stability at the inner membrane.

Keywords: mitochondria; oxidase assembly; oxidative phosphorylation; protein translocation; ribosomes

DOI: https://doi.org/10.1016/j.tcb.2023.02.001

Biol Open. 2023 Mar 15. pii: bio059844. [Epub ahead of print]12(3):

Defective COX1 expression in aging mice liver.

Steffen Witte, Angela Boshnakovska, Metin Özdemir, Arpita Chowdhury, Peter Rehling, Abhishek Aich.

Mitochondrial defects are associated with aging processes and age-related diseases, including cardiovascular diseases, neurodegenerative diseases and cancer. In addition, some recent studies suggest mild mitochondrial dysfunctions appear to be associated with longer lifespans. In this context, liver tissue is considered to be largely resilient to aging and mitochondrial dysfunction. Yet, in recent years studies report dysregulation of mitochondrial function and nutrient sensing pathways in ageing livers. Therefore, we analyzed the effects of the aging process on mitochondrial gene expression in liver using wildtype C57BL/6N mice. In our analyses, we observed alteration in mitochondrial energy metabolism with age. To assess if defects in mitochondrial gene expression are linked to this decline, we applied a Nanopore sequencing based approach for mitochondrial transcriptomics. Our analyses show that a decrease of the Cox1 transcript correlates with reduced respiratory complex IV activity in older mice livers.

Keywords: Ageing; Mitochondria; Nanopore; Transcriptomics

DOI: https://doi.org/10.1242/bio.059844

Arch Biochem Biophys. 2023 Feb 28. pii: S0003-9861(23)00055-3. [Epub ahead of print]737 109556

Mitochondrial elongation factor 4 modulates energy metabolism and promotes breast cancer metastasis by orchestration of mitochondrial translation.

Qianqian Chen, Min Xiao, Fei Dai, Ye Zhang, Jiayun Li, Yanwu Huo, Zhen Huang, Yi Fang, Taotao Wei.

To cope with the requirements of energy and building blocks for rapid proliferation, cancer cells reprogram their metabolic pathways profoundly, especially in oxygen- and nutrients-deficient tumor microenvironments. However, functional mitochondria and mitochondria-dependent oxidative phosphorylation are still necessary for the tumorigenesis and metastasis of cancer cells. We show here that mitochondrial elongation factor 4 (mtEF4) is commonly upregulated in breast tumors compared to adjacent non-cancerous tissues, and is relevant to tumor progression and poor prognosis. Down regulation of mtEF4 in breast cancer cells impairs the assembly of mitochondrial respiration complexes, decreases mitochondrial respiration, reduces ATP production, attenuates the formation of lamellipodia, and suppresses cell motility in vitro and cancer metastasis in vivo. On the contrary, upregulation of mtEF4 elevates the mitochondrial oxidative phosphorylation, which contributes to the migratory capacities of breast cancer cells. mtEF4 also increases the potential of glycolysis, probably via an AMPK-related mechanism. In summary, we provide direct evidences that the aberrantly upregulated mtEF4 contributes to the metastasis of breast cancer by coordinating metabolic pathways.

Keywords: Breast cancer; Glycolysis; Metastasis; Mitochondrial elongation factor 4; Oxidative phosphorylation; Tumorigenesis

DOI: https://doi.org/10.1016/j.abb.2023.109556