Some amphipathic helical peptides are able to form oligomers leading to an increase of the plasma membrane permeability ("pores").
It has been hypothesized that a high oxidative stress level destabilizes the mitochondrial membrane homeostasis and therefore induces the formation of mitochondrial membrane permeability pores releasing pro-apoptotic factors (e.g., cytochrome c).
The former can be initiated by the opening of the inner membrane permeability transition pore or the permeabilization of the outer mitochondrial membrane and release of inter membrane space molecules such as cytochrome c, and Ca+.
Our results demonstrate that TIMP-1-mediated neuroprotection is MMP-independent, at least in part, through modulation of Bcl-2 family of proteins, decreasing of the opening of mitochondrial membrane permeability transition pore (mPTP) and eventually preventing DNA fragmentation.
Mechanically, solanine promotes the opening of mitochondrial membrane permeability transition pore (MPTP) by downregulating the Bcl-2/Bax ratio; thereafter, Cytochrome c and Smac are released from mitochondria into cytosol to process the caspase-3 zymogen into an activated form.
PUMA, known to be transcriptionally activated in ETC‐abnormal fibers (Herbst et al., 2013), is a transcriptional response to p53 activation and influences Bid truncation by binding to Bcl‐2 and inducing membrane permeability transition pore formation.
Oxidative stress can trigger the opening of the mitochondrial membrane permeability transition pore (mPTP) and lead to a significant loss of mitochondrial NAD+ stores and subsequent derangement of cellular energy reserves and intact cellular functions.
In response to metabolic stress, HSD10 protein translocates from the mitochondrial matrix to the inner mitochondrial membrane and this might be important for maintaining mitochondrial integrity as this is an essential site for assembly of the mitochondrial membrane permeability transition pore (Tieu et al, 2004, and unpublished own data).
Many studies have reported impaired mitochondrial respiration [ 13, 14], depletion of hepatocellular ATP levels [ 15, 16], opening of the mitochondrial membrane permeability transition pore [ 17], and increased levels of glutathione disulfide (GSSG) or the ratio of GSSG GSH, suggesting the involvement of an oxidant stress following AAP overdose [ 15, 18].
