Tokyo [Japan], July 22 : Researchers from Tokyo Metropolitan University have shown that the amino acid 5-aminolevulinic acid (5-ALA) helps to restore deficiencies in Complex I (CI), the first of a series of protein complexes that transport electrons and support mitochondrial energization.
They found that when a medicine cocktail containing 5-ALA was administered to fruit flies lacking the homologous protein, their health improved. The majority of mitochondrial diseases are brought on by CI deficiency; the team's findings could result in new treatments.
Adenosine triphosphate (ATP), a chemical fuel that powers a wide range of biochemical processes in our bodies, is produced by mitochondria, a tiny organelle found in cells. Mitochondrial illnesses are caused by issues with ATP production in the mitochondria.
The brain and muscles, which use up more energy than other areas of the body, are severely affected, leading to serious problems such mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a crippling disorder. Sadly, there is presently no cure; nonetheless, researchers continue to search for efficient treatments.
Complex I (CI) deficiency is a common cause of mitochondrial disorders. Complex I is the first of a series of protein complexes that help transport electrons to power reactions in the mitochondria which ultimately lead to the production of ATP. However, this is not the only way in which ATP is made; it is known that Complex II, III, IV and cytochrome c can also provide electrons to the same process, but whether this could be leveraged to counteract CI deficiency was not known.
Now, a team led by Associate Professor Kanae Ando of Tokyo Metropolitan University have shown that certain chemical supplements might help selectively boost CII and CIV to bypass the lack of CI. They studied fruit flies with their equivalent of CI artificially reduced by genetic engineering; flies with this genetic “knockdown” showed problems with their movement and shorter lifespans.
However, they found that feeding them a mixture of 5-aminovulenic acid and sodium ferrous citrate (SFC) helped improve their locomotor functions and neuromuscular junction development. Levels of ATP were also significantly improved, but this was not due to any elevation in the amount of CI.
On closer inspection, the team ascertained that activities of Complex II and IV were elevated and helped bypass the issues associated with CI deficiency. 5-ALA is known to be a precursor to heme, a critical part of the function of Complex II, III, IV and cytochrome c. On being fed 5-ALA, the fruit flies showed a metabolic shift which used the ability of CII and CIV to transport electrons and power the production of ATP. They also noticed that flies with CI deficiency had elevated levels of pyruvate and lactate in their cells, much like human patients with CI deficiency suffering from lactic acidosis. 5-ALA also helped bring down the levels of both.
Despite the severity of mitochondrial disorders, there is as of yet no treatment which addresses the root cause of the vast array of health issues they may cause. The team’s findings promise not only new insight but potentially new therapeutic options for a whole class of deadly diseases.
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