Electron transport through the inner mitochondrial membrane is a crucial process that leads to the release of protons into the intermembrane space, creating a proton motive force. This force induces conformational changes in ATP synthase, specifically in the F0 portion, which spins and causes the gamma subunit of the F1 portion to rotate. This rotation results in conformational changes in the alpha and beta subunits, ultimately facilitating the synthesis and release of ATP from ADP and inorganic phosphate.
In humans, approximately 99% of mitochondrial proteins are encoded by nuclear DNA rather than mitochondrial DNA. Mitochondrial genes are inherited exclusively from the mother, representing a form of non-Mendelian inheritance. While mitochondria can synthesize some of their own proteins, including their own ribosomes and transfer RNA, they do not encode all mitochondrial proteins within their genomes. This limited encoding makes mitochondrial DNA susceptible to mutations, which can impact mitochondrial function.
The introduction of uncoupling agents such as 2,4-Dinitrophenyl (DNP) or FCCP to mitochondria engaged in oxidative phosphorylation inhibits ATP production. These agents work by dissipating the proton gradient across the inner mitochondrial membrane, effectively transporting protons back into the mitochondrial matrix. As a result, while electron transport continues and oxygen consumption remains normal, ATP synthase cannot function effectively due to the lack of proton motive force. Consequently, the phosphate to oxygen (P/O) ratio decreases, indicating a reduced amount of phosphate consumed relative to the amount of oxygen consumed. This decrease reflects the inefficiency in ATP synthesis caused by the disruption of the proton gradient.