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There are many observations suggesting that mitochondrial dysfunction plays a role in ALS (see the source material collection page for mitochondria), but there is no solid theory to connect the mitochondriopathy aspect to the mechanism of the entire disease. On this page I will collect different hypotheses on how the mitochondrial dysfunction might connect to the big picture of ALS.

 

1. Misfolded SOD causing mitochondrial dysfunction

1.1. Blocking of the VDAC1 gate

Misfolded SOD1 is reported to attach to the outer membrane of mitochondrial VDAC1 channel, which is used for transporting ADP into the mitochondrion for production of ATP. Reduced input of ADP would be the cause of inadequate ATP production by mitochondria, causing problems in the energy balance of the cell. 

It has been reported that ADP/ATP ratio in ALS motor neurons is increased, which might be a consequence of ADP being trapped outside the mitochondria (although any failure of the mitochondria to convert ADP to ATP would of course have the same consequence).

 

1.2. Misfolding of SOD1 releases free copper which downregulates mitochondrial function

Copper treatment is reported to increase lactate production in astrocytes. http://www.ncbi.nlm.nih.gov/pubmed/21318477