Difficulties in iron-sulfur cluster formation can lead to iron accumulation in mitochondria

In Friedreich ataxia iron-sulfur clusters are not formed, due to deficiencies in frataxin which results in iron accumulation in mitochondria. The relevant point is that problems in iron-sulfur cluster formation can be associated with iron accumulation in mitochondria and iron toxicity. The point I have been making is that there are difficulties in synthesizing iron-sulfur clusters in many neurological illnesses due to dysregulation of the transsulfuration pathway which synthesizes L-cysteine. L-cysteine supplies sulfur for iron-sulfur cluster formation.

Iron chelators are now being investigated as treatments for Alzheimer’s disease and Parkinson’s disease. If iron is being accumulated in cells in Alzheimer’s disease and Parkinson’s disease due to difficulties in iron-sulfur cluster formation then iron chelators would not be appropriate treatments. Iron-sulfur cluster formation is increased by supplemental iron. Iron chelators by decreasing iron would decrease iron–sulfur cluster formation leading to iron accumulation in mitochondria and iron toxicity.

Coffee and homocysteine

Filtered or unfiltered coffee increases homocysteine levels in healthy individuals whereas caffeine has a much weaker effect on homocysteine levels. Stopping drinking coffee reduces homocysteine levels.

Increased homocysteine levels point to decreased levels of L-cysteine which is synthesized from homocysteine. With decreased synthesis of L-cysteine iron-sulfur cluster formation could be dysregulated which could upset many biological processes. Increased homocysteine levels could could affect DNA methylation. In schizophrenia there is a positive association between plasma homocysteine and DNA methylation. Difficulties due to coffee could take years to develop due to hypermethylation of genes taking years to develop.