atp is produced in the intermembrane space of mitochondria.
atp is produced in the intermembrane space of mitochondria.
what is produced in the intermembrane space of mitochondria?
atp
cytochrome c release is proposed to take place in one of two ways. firstly, the permeability transition pore (ptp) when the mitochondria receives a death inducing signal, and releases intermembrane space proteins (12). the ptp is composed of the voltage-dependent anion channel (vdac), the inner membrane protein adenine nucleotide translocator (adnt) and the matrix protein cyclophilin d (cyd) (12). this pore causes the mitochondria to swell and the outer mitochondrial membrane to rupture (diamond & mccabe, 2007). with this change in permeability, proteins such as cytochrome c are released into the cytosol (12). this change likely causes the mitochondrial permeability transition (mpt), where the mitochondrial transmembrane potential collapses, and atp production ceases (12). the inhibition of this method by the pharmaceutical agent cyclosporine a (csa), lead to the discovery of the second pathway (13). the second method of cytochrome c release is independent of the ptp and involves only the vdac. members of the bcl-2 family of pro-apoptotic proteins can induce the opening of the vdac (12). this will cause the same release of intermembrane space proteins, including cytochrome c, and the subsequent mpt to occur (12).
apoptosome
small tim proteins are synthesised lacking a cleavable presequence, but instead containing internal targeting information and need to be imported to the intermembrane space. the intermembrane space import and assembly machinery (mia) is believed to mediate transport of the small tim precursors into the intermembrane space subcompartment. mia is composed of two main essential cysteine-rich proteins; mia40 and erv1. mia40 is also referred to as tim40 in yeast and deficiency of mia40 has been reported to affect import of the small tims. mia40 is anchored to the mitochondrial inner membrane via an n-terminal hydrophobic segment, exposing a large domain to the intermembrane space. it contains 6 conserved cysteine residues, which allow the binding of incoming tim precursor proteins. following import of small tim proteins into the intermembrane space mia40 interacts with small tim proteins via disulfide bonds. following isomerisation of the disulfide bridge, the polypeptide is released. mia40 which is now in reduced state, is then oxidised by erv1. this oxidation step is vital to facilitate further rounds of precursor protein import. without erv1 activity, reduced mia40 accumulates and is in inactive conformation. interaction between the incoming precursor proteins, mia40 and erv1, is maintained as a result of a flow of electrons that are transferred from the incoming protein to mia40 and from reduced mia40 to oxidised erv1. precursors are then released in oxidised state and form disulfide bridges which prevents their escape out of the intermembrane space. small tim proteins are then maintained in active conformation within the intermembrane space by hot13 (helper of tims). it is possible that hot13 may have reducing effects on small tim proteins as they counterbalance the harmful effects that oxidative agents exhibit.
tim9-tim10 complex