Revisiting trends on mitochondrial mega-channels for the import of proteins and nucleic acids

The discovery of very large channels in the two membranes of mitochondria represented an astonishing finding and a turning point in the awareness of these conspicuous energy-generating organelles. Sizable channels are at the crossroads of important cellular pathways and mitochondrial functions like biogenesis, signaling, secretion, compartmentalization or apoptosis. The integrative approach that combines electrophysiological methods with biochemical and genetic alterations has been decisive to tackle the structure-function relationship of mitochondrial mega-channels. In this review we will give a short account of our joint effort to correlate the existence of large conductance channels in the two membranes of mitochondria with a precise function. In particular, we will focus on the import of proteins and nucleic acids. An analysis of the character of the aqueous pores through which these two types of macromolecules enter mitochondria has been attained, and an up-to date survey of the developments reached in these investigations will be presented. An overlook of the import pathways for proteins and nucleic acids into mitochondria will be outlined. Although this research area is rapidly developing, many issues remain shrouded in uncertainties. A special emphasis will be prone to the not yet entirely settled synergies between different protein translocases.