Protein import into mitochondria: origins and functions today (Review)

Abstract

Mitochondria are organelles derived from alpha-proteobacteria over the course of one to two billion years. Mitochondria from the major eukaryotic lineages display some variation in functions and coding capacity but sequence analysis demonstrates them to be derived from a single common ancestral endosymbiont. The loss of assorted functions, the transfer of genes to the nucleus, and the acquisition of various 'eukaryotic' proteins have resulted in an organelle that contains approximately 1000 different proteins, with most of these proteins imported into the organelle across one or two membranes. A single translocase in the outer membrane and two translocases in the inner membrane mediate protein import. Comparative sequence analysis and functional complementation experiments suggest some components of the import pathways to be directly derived from the eubacterial endosymbiont's own proteins, and some to have arisen 'de novo' at the earliest stages of 'mitochondrification' of the endosymbiont. A third class of components appears lineage-specific, suggesting they were incorporated into the process of protein import long after mitochondria was established as an organelle and after the divergence of the various eukaryotic lineages. Protein sorting pathways inherited from the endosymbiont have been co-opted and play roles in intraorganelle protein sorting after import. The import apparatus of animals and fungi show significant similarity to one another, but vary considerably to the plant apparatus. Increasing complexity in the eukaryotic lineage, i.e., from single celled to multi-cellular life forms, has been accompanied by an expansion in genes encoding each component, resulting in small gene families encoding many components. The functional differences in these gene families remain to be elucidated, but point to a mosaic import apparatus that can be regulated by a variety of signals.

Isthmin targets cell-surface GRP78 and triggers apoptosis via induction of mitochondrial dysfunction

“…Co-IP experiment revealed no evidence that ISM binds to TOM20, the first receptor involved in recognizing the targeting sequence of a mitochondria protein in TOM complex that is known to mediate the import of mitochondria proteins through the outer membrane (data not shown). 35,36 In addition, no member of TOM complex was identified as binding partners for ISM in mitochondria (Figure 4e). Therefore, ISM is unlikely to be imported into mitochondria through TOM complex.…”

Refining the Definition of Plant Mitochondrial Presequences through Analysis of Sorting Signals, N-Terminal Modifications, and Cleavage Motifs

“…This has been highlighted as a case of convergent evolution of a receptor that uses a similar mechanism of binding to recognize presequences (Lister and Whelan, 2006). Although structural studies reveal the importance of hydrophobic residues for presequence binding, several studies on yeast, mammals, and plants reveal an important role for positively charged residues in presequences for import into mitochondria (Lister et al, 2005;Neupert and Herrmann, 2007). These positively charged residues may play a role in positioning the amphiphilic a-helix for binding to Tom20 and also in subsequent translocation into and across the pores forming proteins of the TOM and TIM (for translocase of the inner membrane) complexes.…”

Protein Translocase of Mitochondrial Inner Membrane in Trypanosoma brucei

“…Tom6, Tom7, and Tom22 are involved in structural assembly of the complex. There are two TIMs (TIM23-17 and TIM22-54) in the mitochondrial inner membrane (MIM) in fungi to mammals (3)(4)(5). The TIM23-17 complex imports N-terminal mitochondrial targeting signal (MTS)-containing proteins as well as an adjacent hydrophobic sorting signal-containing proteins destined to the mitochondrial matrix and the MIM, respectively (8,9).…”

“…Protein translocases of mitochondrial outer and inner membranes (TOMs 3 and TIMs, respectively) have been extensively characterized in fungi and higher eukaryotes (3)(4)(5). TOM is a multisubunit protein complex that is responsible for import of virtually all nucleus-encoded proteins through the mitochondrial outer membrane (MOM) (6,7).…”