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Review
. 2022 Jan 6:12:806426.
doi: 10.3389/fphys.2021.806426. eCollection 2021.

Coordinated Translocation of Presequence-Containing Precursor Proteins Across Two Mitochondrial Membranes: Knowns and Unknowns of How TOM and TIM23 Complexes Cooperate With Each Other

Marcel G Genge  1 , Dejana Mokranjac  1
Affiliations
Review

Coordinated Translocation of Presequence-Containing Precursor Proteins Across Two Mitochondrial Membranes: Knowns and Unknowns of How TOM and TIM23 Complexes Cooperate With Each Other

Marcel G Genge et al. Front Physiol. .

Abstract

The vast majority of mitochondrial proteins are encoded in the nuclear genome and synthesized on cytosolic ribosomes as precursor proteins with specific mitochondrial targeting signals. Mitochondrial targeting signals are very diverse, however, about 70% of mitochondrial proteins carry cleavable, N-terminal extensions called presequences. These amphipathic helices with one positively charged and one hydrophobic surface target proteins to the mitochondrial matrix with the help of the TOM and TIM23 complexes in the outer and inner membranes, respectively. Translocation of proteins across the two mitochondrial membranes does not take place independently of each other. Rather, in the intermembrane space, where the two complexes meet, components of the TOM and TIM23 complexes form an intricate network of protein-protein interactions that mediates initially transfer of presequences and then of the entire precursor proteins from the outer to the inner mitochondrial membrane. In this Mini Review, we summarize our current understanding of how the TOM and TIM23 complexes cooperate with each other and highlight some of the future challenges and unresolved questions in the field.

Keywords: TIM23 complex; TOM complex; TOM-TIM23 contacts; intermembrane space; mitochondria; precursor transfer; presequence pathway; protein translocation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the TOM and TIM23 complexes. The TOM complex consists of the receptors, Tom20, Tom22, and Tom70, and a channel unit, formed by Tom40, associated with three small proteins Tom5, Tom6 and Tom7. It possesses cis and trans presequence-binding sites. The TIM23 complex can be functionally divided into receptors, translocation channel and import motor – Tim23, Tim17, Tim50, Tim44, Tim14, Tim16, mtHsp70 (Ssc1), Mge1, Tim21, Mgr2, and Pam17. See text for details. OM, outer membrane; IMS, intermembrane space; IM, inner membrane.
Figure 2
Figure 2
TOM and TIM23 cooperation during precursor translocation across two mitochondrial membranes. (A) Subunits implicated in TOM and TIM23 cooperation are highlighted in red. Dashed lines represent identified interaction points. (B–D) Current working model for transfer of precursors from the TOM to the TIM23 complex. See text for details. OM, outer membrane; IMS, intermembrane space; IM, inner membrane.
See this image and copyright information in PMC

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