Meet Tom

We have just seen that bacterial cells were preadapted for the formation of mitochondria. More specifically, one out of every twenty bacterial proteins harbors the equivalent of the mitochondrial targeting sequence which is needed for entry into the mitochondria. But this story gets more interesting. To appreciate the twist that comes next, let’s step back to make sure we can visualize the process of transporting mitochondrial proteins into the mitochondria.

First, like gram negative bacteria, the mitochondria have two membranes:

We want to focus on the outer membrane, as this is where the mitochondrial proteins, synthesized by the ribosomes in the cell’s cytoplasm, must be targeted for entry into the mitochondria.

Mitochondrial proteins are sent to something called the TOM complex that is found in the outer membrane. The figure below shows a simplified version of this complex that is composed of a receptor, that binds the mitochondrial targeting sequence on mitochondrial proteins, and shuttles it to the channel for entry into the mitochondria (TIM is the inner membrane transporter).

The figure below provides more detail:

You can see the mitochondrial protein on the top with its exposed mitochondrial targeting sequence (the + signs near the N). The mitochondrial targeting sequence binds to the receptor (R) which passes the protein to the TOM channel (shown as GIP in this picture). The protein is then threaded through both TOM and TIM, using the same proton gradient that mitochondria generate for their ATP synthases.

Now, take a look at a more detailed figure:

As you can see, TOM is composed of multiple proteins. Tom7, Tom22, and Tom40 are the core elements of this complex, where Tom40 form the pore itself and is likely to be the descendent of bacterial porins (protein pores found in the outer membranes of gram negative bacteria).

It turns out that the mitochondrial targeting sequence interacts with multiple components of this system:

The intracellular sorting of newly synthesized precursor proteins (preproteins) to mitochondria depends on the “mitochondria-targeting sequence” (MTS), which is located at the amino termini of the preproteins. MTS is required, however, not only for targeting newly synthesized preproteins to mitochondria, but also for all the following steps along the mitochondrial protein import pathway. MTS of nascent preproteins is first recognized by a cytoplasmic molecular chaperone, MSF, and then by Tom70 and Tom20 of the mitochondrial outer membrane receptor complex, Tom5 and Tom40 of the outer membrane protein translocation machinery, Tim23 of the inner membrane protein translocation machinery, and finally the processing peptidase, MPP, in the matrix. MTS is a multi-role sorting sequence which specifically interacts with various components along the mitochondrial protein import pathway. Recognition of MTS at multiple steps during the import of preproteins may contribute to the strict sorting of proteins destined for mitochondria.

From: Omura, T. 1998. Mitochondria-Targeting Sequence, a Multi-Role Sorting Sequence Recognized at All Steps of Protein Import into Mitochondria J. Biochem 123: 1010-1016.

The player I want to focus on is Tom20. Why? Because Tom20 is the receptor protein that snags the mitochondria targeting sequence. Tom20 is not essential, as yeast strains have been constructed where Tom20 was removed and the yeast remain viable. This means that the receptor simply enhances the efficiency of the transport process.

It’s time for the story to get more interesting….

3 responses to “Meet Tom

  1. Tipsy McStagger


    a few questions:

    1) If only 1 in 20 bacterial proteins even have the MTS, how would – upon the initial endosymbiosis – the new mitochondria ‘know’ to only send genetic elements to the hosts DNA that have the ability to bind with MTS…. for the eventual allowing of it to enter into the mitochondria.

    2) Isn’t the outer membrane of the mitochondria from the host’s original membrane (formed from the vesicle that the host would have ‘placed’ the aerobic bacterium in)? If so, how would such an elaborate pathway exist that would allow this protein, with attached MTS, to be able to be granted access over two different different membranes? The outer (host) and the inner (original aerobic bacterium)?

    3) My understanding of bacteria might be off. But I always thought that prokaryotes are noted by their lacking of membrane bound organelles. What would a bacterial protein need an proto-MTS sequence for it if there is no membrane to traverse.


  2. Excellent questions! I have to run now, but I’ll get to them as soon as I can.

  3. Let me take stab at these good questions:

    1. The new mitochondria would not need to know. The pre-existence of the MTS would guide the blind watchmaker by setting up a selective pressure for recombination processes to paste MTS sequences on the front end of proteins needed by the mitochondria. Also, it is possible that in the original state, only mitochondrial proteins had the MTS, but this state has been erased in bacteria over the last few billion years.

    2. I wondered if anyone else would notice that! Yes, it would seem we have two choices. Either the outer membrane proteins from gm negative bacteria were moved to the host’s vesicle membrane or the outer membrane of the mitochondria is descended from the outer membrane of the bacteria. I’d favor the latter explanation, but that does take away from the simplicity of the phagocytosis mechanism of original acquisition. We have ourselves a new mystery.

    3. Another good question. While bacteria don’t have membranous organelles, gm- bacteria have five possible destinations for their proteins:

    a. inside the cytoplasm
    b. insert into the inner membrane
    c. between the inner and outer membrane
    d. insert into the outer membrane
    e. secreted out of the cell (past the outer membrane).

    It is possible the MTS in bacteria participate in movement across the outer or inner membrane, but yes, no one seems to know what the MTS is doing in bacteria as I don’t think anyone has looked.

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