Abstract

Mitochondrial membrane proteins play an essential role in all major mitochondrial functions. The respiratory complexes of the inner membrane are key for the generation of energy. The carrier proteins for the influx/efflux of essential metabolites to/from the matrix. Many other inner membrane proteins play critical roles in the import and processing of nuclear encoded proteins (∼99% of all mitochondrial proteins). The outer membrane provides another lipidic barrier to nuclear-encoded protein translocation and is home to many proteins involved in the import process, maintenance of ionic balance, as well as the assembly of outer membrane components. While many aspects of the import and assembly pathways of mitochondrial membrane proteins have been elucidated, many open questions remain, especially surrounding the assembly of the respiratory complexes where certain highly hydrophobic subunits are encoded by the mitochondrial DNA and synthesised and inserted into the membrane from the matrix side. This review will examine the various assembly pathways for inner and outer mitochondrial membrane proteins while discussing the most recent structural and biochemical data examining the biogenesis process.

Highlights

  • Mitochondria are critically important for metabolism and a whole range of cellular functions, while they play an essential role in programmed cell death

  • The dimeric form of Tom40 lacking Tom22 acts as an assembly intermediate allowing the dynamic exchange of new TOM subunits with the trimeric complex containing older subunits (Shiota et al, 2015; Araiso et al, 2021)

  • More work is needed to understand SAM-mediated outer membrane assembly in humans given that yeast TOM cannot be assembled by human SAM (Wang et al, 2021)

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Summary

Targeting and Insertion of Membrane Proteins in Mitochondria

Specialty section: This article was submitted to Cellular Biochemistry, a section of the journal Frontiers in Cell and Developmental. Mitochondrial membrane proteins play an essential role in all major mitochondrial functions. Many other inner membrane proteins play critical roles in the import and processing of nuclear encoded proteins (∼99% of all mitochondrial proteins). While many aspects of the import and assembly pathways of mitochondrial membrane proteins have been elucidated, many open questions remain, especially surrounding the assembly of the respiratory complexes where certain highly hydrophobic subunits are encoded by the mitochondrial DNA and synthesised and inserted into the membrane from the matrix side. This review will examine the various assembly pathways for inner and outer mitochondrial membrane proteins while discussing the most recent structural and biochemical data examining the biogenesis process

INTRODUCTION
Mitochondrial Membrane Protein Biogenesis
OUTER MEMBRANE PROTEIN BIOGENESIS
PROTEIN ASSEMBLY BY THE TRANSLOCON OF THE INNER MEMBRANE

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