Elucidating the mechanism
In addition, they have been shown to be involved in mitophagy.
While studies of PINK1 and Parkin have been important, there are still many unanswered questions about the molecular mechanisms of mitochondrial quality control.
Initially, metformin was believed to interfere with complex 1 of the respiratory chain leading to a reduced ratio of [ATP]/[ADP.
AMP] activating the enzyme AMP-activated protein kinase (AMPK).
The assumption that the effects of metformin are exclusively mediated by AMPK has recently been challenged by genetic loss-of-function experiments.
Since then it has been hypothesized that metformin inhibits hepatic gluconeogenesis by interfering with the c AMP/PKA pathway acting as a glucagon antagonist.
For 60 years, biguanides have been one of the few effective therapeutics in reducing blood glucose levels.
Diabetes type 2 patients are insensitive to insulin, a condition that leads to reduced glucose uptake by cells and, subsequently, to high concentration of glucose in the blood.
Because mitochondria supply most of the chemical energy for the cell, they are critical for the normal function of high-energy tissues such as neurons.