The field of mitochondrial
ion channels has undergone a rapid development during the last three decades, due to the molecular identification of some of the channels residing in the outer and inner membranes. Relevant information about the function of these channels in physiological and pathological settings was gained thanks to genetic models for a few, mitochondria-specific channels. However, many
ion channels have multiple localizations within the cell, hampering a clear-cut determination of their function by pharmacological means. The present review summarizes our current knowledge about the ins and outs of mitochondrial
ion channels, with special focus on the channels that have received much attention in recent years, namely, the
voltage-dependent anion channels, the permeability transition pore (also called
mitochondrial megachannel), the
mitochondrial calcium uniporter and some of the inner membrane-located
potassium channels. In addition, possible strategies to overcome the difficulties of specifically targeting mitochondrial channels versus their counterparts active in other membranes are discussed, as well as the possibilities of modulating channel function by small
peptides that compete for binding with
protein interacting partners. Altogether, these promising tools along with large-scale chemical screenings set up to identify new, specific channel modulators will hopefully allow us to pinpoint the actual function of most mitochondrial
ion channels in the near future and to pharmacologically affect important pathologies in which they are involved, such as neurodegeneration, ischaemic damage and
cancer. LINKED ARTICLES: This article is part of a themed section on Mitochondrial Pharmacology: Featured Mechanisms and Approaches for
Therapy Translation. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.22/issuetoc.