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Mitochondrial proteome has been calculated
around a thousand proteins in a standard humans.
Mitochondria have four compartments,
each with a distinct compliment of proteins.
Around 500 different proteins are present in the matrix,
including the TCA cycle enzymes and
numerous factors that mediate transcription and replication of the mitochondrial DNA.
The inner membrane also has a large number of distinct proteins,
including those that function in electron transport.
The outer membrane has a number of peripheral and integral membrane proteins,
most notably the protein VDAC,
an intermembrane space, again
a number of different proteins,
but most notably Cytochrome C that functions in the electron transport chain.
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99 percent of these proteins are encoded for in the nucleus,
translated on ribosomes in the cytosol,
and make their way to the mitochondria post-translationally.
The import of these proteins is mediated by
four molecular machines that are
integrated into the outer membrane and the inner membrane.
These machines are: the TOM complex,
the TIM23 complex situated in the inner membrane,
another complex in the inner membrane referred to as
the TIM22 complex, and the SAM complex.
This talk covers the targeting sequences
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that can lead proteins to mitochondria and the four translocases
in the outer and the inner mitochondrial membranes that mediate
the correct sorting of these proteins into the appropriate sub-mitochondrial compartment.
We'll then discuss whether the protein import pathway that we understand in yeast and
in humans reflects the protein import pathway that's used by other eukaryotes.
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This diagram shows the four machines,
molecular machines, that mediate protein import into mitochondria.
In particular, it shows that each one is made of
several different components and the numbers reflect the size of each of the subunits,
in terms of kilodaltons.
Each of proteins that has to make its way into the mitochondria
will first interact with the TOM complex in the outer membrane,
and the possible pathways that an incoming protein might
take are reflected by the arrows shown on the diagram.
The classic mitochondrial targeting sequence is an
amphipathic basic helix that forms at the N terminus of a precursor protein.
These precursors are synthesized on ribosomes
and then recognized by the TOM complex shaded yellow here.
There are specific receptor subunits in the TOM complex,
in particular, TOM20 and TOM 22,
that can interact with the basic amphipathic helix of the protein and another receptor,
TOM70, that combines to the unfolded regions in the rest of the polypeptide.
