Mitochondria associated membranes

These membranes are involved in import of certain lipids from the ER to mitochondria and in regulation of calcium homeostasis, mitochondrial function, autophagy and apoptosis.

This interaction is important for rapid uptake of calcium by mitochondria through Voltage dependent anion channels (VDACs), which are located at the outer mitochondrial membrane (OMM).

Mitochondrial outer membrane permeabilization (MOMP), is a reason of the higher matrix Ca2+ levels, which is acts as a trigger for apoptosis.

Permeability transition pore (PTP) opening induces mitochondrial swelling and outer membrane of the mitochondria (OMM) rupture.

Caspase-activating factors induced by cytochrome C to bind to the IP3R, this will result in higher Ca2+ transfer from the ER to the mitochondria, amplifying the apoptotic signal.

Also with regard to the role in MAMs in phospholipid metabolism, patients diagnosed with AD have been reported to show alterations in levels of Phosphatedylserine and phostphatedylethanolamine in the ER and mitochondria respectively, this leads to the intracellular tangles containing hyperphosphorylated forms of the microtubule‐associated protein tau within tissues.

In normal conditions, these genes are believed to be responsible for the cells ability to degrade mitochondria that has been rendered nonfunctional in a process known as mitophagy.

The wild-type gene that codes for α-Syn promotes the physical junction between ER and mitochondria by binding to the lipid raft regions of the MAM.

However, the mutant form of this gene has a low affinity to the lipid raft regions, thereby diminishing the contact between the ER and mitochondria and causing accumulation of α-Syn in Lewy bodies which is a major characteristic of PD.

Area-Gomez E, de Groof AJ, Boldogh I, Bird TD, Gibson GE, Koehler CM, Yu WH, Duff KE, Yaffe MP, Pon LA, Schon EA.