Novel Channels of the Outer Membrane of Mitochondria: Recent Discoveries Change Our View

Checchetto, Vanessa; Szabó, Ildikò

doi:10.1002/bies.201700232

Cited by 13 publications

(7 citation statements)

References 59 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The existence of CICs and K ir channels, both small‐conductance channels, in the OMM challenges the traditional view that the outer membrane forms an unspecific size‐exclusion filter for the flux of small hydrophilic molecules (Becker and Wagner, ). In yeast mitochondria, the recent identification of three novel ion channels in the OMM with unknown substrate specificity (Kruger et al ., ) points to the same conclusion (Checchetto and Szabo, ). Whether homologues of the yeast OMM channels also operate in mammalian OMM is still an open question as is the pharmacology of these channels.…”

Section: Mitochondrial Outer Membrane (Omm) Channelssupporting

confidence: 76%

Pharmacological modulation of mitochondrial ion channels

Leanza

Checchetto

Biasutto

et al. 2019

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Mitochondrial Outer Membrane (Omm) Channelssupporting

confidence: 76%

Pharmacological modulation of mitochondrial ion channels

Leanza

Checchetto

Biasutto

et al. 2019

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Given the high conductance of porins, the MOM has long been viewed as a molecular sieve allowing the flux of several molecules without the need of specific transport systems. However, this view has recently been changed, at least in yeast, following the discovery of several new, solute-specific channels in the MOM [51,52,53]. Independently of the exact nature of the molecules crossing through VDAC1, this channel received much attention in the context of tumorigenesis as well as of apoptotic signaling (Figure 4).…”

Section: Defective Mitochondrial Outer Membrane Permeabilization Amentioning

confidence: 99%

Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Peruzzo

Szabó

2019

Cancers

Self Cite

View full text Add to dashboard Cite

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

show abstract

“…The extrinsic and intrinsic pathways are the two major pathways regulating apoptosis, which are also known as death receptor pathways and mitochondrial pathways ( 13 , 15 ). Mitochondria are two-layered membrane organelles that are present in cells, and are the main organelles that maintain homeostasis within cells and the main site for aerobic respiration of cells ( 16 ). The destruction of mitochondria is an important feature of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway

Huang

et al. 2018

Oncol Rep

View full text Add to dashboard Cite

Ursodeoxycholic acid (UDCA) is a type of hydrophilic bile acid extracted from animal bile with a wide range of biological functions. The present results demonstrated that UDCA could effectively inhibit the proliferation of two human melanoma cell line (M14 and A375) with time- and concentration-dependence. Following exposure to various concentrations of UDCA, M14 cells exhibited typical morphological changes and weaker ability of colony forming. Flow cytometry analysis demonstrated that UDCA could induce a decrease of mitochondrial membrane potential and an increase in reactive oxygen species (ROS) levels in M14 cells. The cell cycle was arrested in the G2/M phase, which was confirmed by the decrease of cyclin-dependent kinase 1 and cyclinB1 at the protein level. However, when M14 cells were treated with UDCA and Z-VAD-FMK (caspase inhibitor) synchronously, the apoptosis rate of the cells was reduced significantly. In addition, it was demonstrated that UDCA induced apoptosis of human melanoma M14 cells through the ROS-triggered mitochondrial-associated pathway, which was indicated by the increased expression of cleaved-caspase-3, cleaved-caspase-9, apoptotic protease activating factor-1, cleaved-poly (ADP-ribose) polymerase 1 and the elevation of B cell lymphoma-2 (Bcl-2) associated X protein/Bcl-2 ratio associated with apoptosis. Therefore, UDCA may be a potential drug for the treatment of human melanoma.

show abstract

Novel Channels of the Outer Membrane of Mitochondria: Recent Discoveries Change Our View

Cited by 13 publications

References 59 publications

Pharmacological modulation of mitochondrial ion channels

Pharmacological modulation of mitochondrial ion channels

Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Apoptosis induced by ursodeoxycholic acid in human melanoma cells through the mitochondrial pathway

Contact Info

Product

Resources

About