Dear colleagues, 

It is well-understood that mitochondria are essential organelles for cellular life.  Mitochondria function in many processes such as the biosynthesis of steroids and heme, intermediate metabolism, calcium and iron homeostasis, and the production of energy in the form of ATP by the oxidative phosphorylation system (OXPHOS). Substrate oxidation by respiratory complexes generate the protonmotive force that drives ATP synthesis by the F1FO-ATPase and, consistent with this activity, mitochondria contribute significantly to cellular reactive oxygen species (ROS) production. Given their involvement in the regulation of redox signaling when ROS imbalance occurs, oxidative stress can trigger programmed cell death through the formation of the mitochondrial permeability transition pore (mPTP).

Considering the numerous roles that mitochondria play in eukaryotic cells, mitochondrial dysfunction is responsible for a wide variety of disease states. Mutations in genes, residing within either the mitochondrial or nuclear genome, which encode the mitochondrial proteome are responsible for alterations in mitochondrial subunits, and assembly factors of respiratory complexes and/or supercomplexes. Such alterations can affect multiple tissues, but principally those that have increased energy requirements to perform their functions, for example, muscle, heart, and neuron tissues. Mutations that alter the function of mitochondrial respiratory complexes and the synthesis of ATP lead to a heterogeneous group of diseases such as mitochondrial encephalomyopathy with lactic acid and stroke-like episodes (MELAS), Leigh syndrome (LS), Leber hereditary optic neuropathy (LHON), and cerebral cardiomyopathy. Proper functioning of OXPHOS is therefore essential for maintenance of cellular homeostasis.

The focus of this Special Issue is to understand the molecular mechanisms of mitochondrial complexes during OXHPOS which ensure appropriate mitochondrial function. The characterization of molecular mechanisms involved in physiological and/or pathophysiological conditions will provide useful information as to their potential use as specific pharmacological targets, as well as better understanding the pathological conditions stemming from their dysregulation. 

Dr. Salvatore Nesci,

Guest Editor