Novel interactions of mitochondria and reactive oxygen/nitrogen species in alcohol mediated liver disease

Figure 1 Superoxide production and reactive nitrogen species reactions in mitochondria. During electron transfer superoxide (O₂^●–) is generated within Complexes I (b, c) and III (a) due to the presence of stable semiquionine anion species. Solid arrows illustrate forward electron flow, whereas dashed arrows indicate reverse electron flow through Complex II to increase O₂^●– production in ComplexI(c). O₂^●– dismutation to hydrogen peroxide (H₂O₂) by manganese superoxide dismutase (MnSOD) affects cellular redox signaling pathways (d). Increased iNOS expression leads to diffusion of nitric oxide (NO) into mitochondria where it inhibits cytochrome c oxidase (e), which increases O₂^●– generation.

Figure 2 Overlapping alterations to the liver mitochondrial proteome contribute to the development of alcohol-induced liver disease. This figure illustrates the concept that there is a unique mitochondrial sub-proteome that when altered by chronic alcohol mediated mtDNA/ribosome damage, increased ROS/RNS production, and energy deficits contribute to the development of alcohol hepatotoxicity. These alterations involve changes in both protein levels (panel A) and post-translational modifications (PTMs, panel B) to this susceptible population of mitochondrial proteins.