Amphipathic N-terminal signal for mitochondrial matrix import
A protein bound for the mitochondrial matrix (the innermost space) usually carries an amphipathic sequence, part water-loving and part water-avoiding, at its N-terminus, the start of the chain.
Remember
The usual label for a protein bound for the mitochondrial matrix is an amphipathic sequence at its N-terminus, recognised at the outer membrane and cut off after import.
Most mitochondrial proteins are nuclear-encoded, which means they are made from nuclear genes on ribosomes in the cytoplasm and only then imported. A nuclear-encoded protein bound for the mitochondrial matrix needs an address label to reach it.
The usual label is an amphipathic sequence of about 10 to 80 amino acids at the N-terminus, the start of the chain. Amphipathic means having both a water-loving and a water-avoiding part: the stretch has positively charged amino acids on one face and hydrophobic (water-avoiding) amino acids on the other. Think of the signal as positive and oily at the same time.
Chaperones (proteins that stop a chain folding too early) keep the chain unfolded, so receptors on the outer mitochondrial membrane can recognise the signal. A channel called TOM (translocase of the outer membrane) lets the chain through. For the matrix, a second channel, TIM (translocase of the inner membrane), takes over. This stage needs energy and a membrane potential, an electrical gradient across the inner membrane.
The signal is only an address label, so it is cut off once the protein has crossed the inner membrane. An enzyme called mitochondrial processing peptidase removes it, and the protein then folds. If the signal is lost, the protein is not recognised at the outer membrane and stays in the cytoplasm, even though the mitochondrial membranes and channels are normal.
Other organelles use different labels. The endoplasmic reticulum uses a hydrophobic signal sequence at the N-terminal end, whereas peroxisomes (another organelle) use serine-lysine-leucine at the C-terminal end, the opposite end of the chain.
Key facts
- Signal
- usually an amphipathic sequence of about 10 to 80 amino acids at the N-terminus, the start of the chain.
- Route
- the unfolded chain crosses the outer membrane through TOM, then the inner membrane through TIM, a step that needs a membrane potential and energy.
- State on entry
- the protein is imported unfolded, held by chaperones, and folds after the signal is removed.
- Signal removal
- mitochondrial processing peptidase cuts the signal off inside the matrix.
- Lost signal
- a matrix protein without its signal is not recognised at the outer membrane and stays in the cytoplasm.
- Contrast
- peroxisomes use serine-lysine-leucine as a C-terminal label instead of the N-terminal one.
Exam traps
- A C-terminal run of serine, lysine and leucine is a genuine address label, but it belongs to the peroxisome, and a mitochondrial matrix protein is normally labelled at the N-terminal end instead.
- Losing the membrane potential would block import at the inner membrane, but a protein that has lost its signal fails earlier, at recognition on the outer membrane.
- Stop-transfer sequences, extra signals that can halt a protein in the inner membrane instead of letting it pass into the matrix, only act once import has begun, so a protein that has lost the signal that starts import does not get far enough for them to act.
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