The permeability transition pore signals apoptosis by directing Bax translocation and multimerization

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
FrancesaA De GiorgiFrançois Ichas

Abstract

Mitochondria are key players of apoptosis and can irreversibly commit the cell to death by releasing cytochrome c (Cyt.c) to the cytosol, where caspases 9 and 3 subsequently get activated. Under conditions of oxidative stress, opening of the mitochondrial permeability transition pore (PTP) represents an early trigger and is crucial in causing Cyt.c release. To account for the latter, current models propose that PTP gating would result, as is the case in vitro, in the rupture of the outer mitochondrial membrane caused by mitochondrial matrix swelling. Using live cell imaging and recombinant fluorescent probes based on the green fluorescent protein (GFP) and its mutants, we report that directed repetitive gating of the PTP triggers a delayed Cyt.c efflux, which is not associated with mitochondrial swelling. Instead, subcellular imaging shows that PTP opening signals the redistribution of the cytosolic protein Bax to the mitochondria, where it secondarily forms clusters that appear to be a prerequisite for Cyt.c release. Fluorescence resonance energy transfer imaging further reveals that Bax clustering coincides with the formation of Bax multimers. We conclude that the PTP is not itself a component of the Cyt.c release machinery, ...Continue Reading

References

May 1, 1990·The American Journal of Physiology·T E Gunter, D R Pfeiffer
Jun 9, 1995·The Journal of Biological Chemistry·W H YuM Forte
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·L M LoewF S Fay
Jan 7, 1998·The Journal of Cell Biology·K G WolterR J Youle
Apr 17, 1998·Biophysical Journal·J HüserL A Blatter
Aug 26, 1998·Trends in Cell Biology·D Green, G Kroemer
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·G BasañezR J Youle
Jul 17, 1999·European Journal of Biochemistry·N JohnsonM Crompton
Sep 22, 1999·European Journal of Biochemistry·P BernardiF Di Lisa
Aug 10, 2000·Trends in Cell Biology·S Desagher, J C Martinou
Feb 13, 2001·Trends in Biochemical Sciences·P BernardiM Forte
Mar 30, 2001·The Journal of Biological Chemistry·V MikhailovP Saikumar
Oct 3, 2002·Journal of Neurochemistry·Allen S MandirTed M Dawson

❮ Previous
Next ❯

Citations

Sep 22, 2005·Cancer Chemotherapy and Pharmacology·Ryungsa KimKazuaki Tanabe
Jul 11, 2006·Apoptosis : an International Journal on Programmed Cell Death·Jafar NaderiSiyaram Pandey
Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Kathleen W Kinnally, Bruno Antonsson
Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Andrea Rasola, Paolo Bernardi
Apr 25, 2007·Apoptosis : an International Journal on Programmed Cell Death·Stefan Grimm, Dieter Brdiczka
Jun 1, 2005·Biochemical and Biophysical Research Communications·Ryungsa Kim
Mar 20, 2004·Pharmacology & Therapeutics·Amere Subbarao Sreedhar, Peter Csermely
Oct 3, 2002·Journal of Neurochemistry·Anatoly A StarkovGary Fiskum
Apr 7, 2009·The Journal of Biological Chemistry·Jean François DumasEric Fontaine
Aug 24, 2005·Antioxidants & Redox Signaling·Ronald JemmersonNickolay Brustovetsky
Dec 17, 2005·Antioxidants & Redox Signaling·Renu A Kowluru
Sep 22, 2006·Antioxidants & Redox Signaling·Nathan R BradyRoberta A Gottlieb
Mar 18, 2005·Molecular Biology of the Cell·Laurent M DejeanKathleen W Kinnally
Oct 19, 2006·Journal of the National Cancer Institute·Arata TomiyamaChifumi Kitanaka
May 15, 2007·Plastic and Reconstructive Surgery·Ewa J WitortSergio Capaccioli
Apr 21, 2005·Science's STKE : Signal Transduction Knowledge Environment·Yisang Yoon
Nov 6, 2012·Oxidative Medicine and Cellular Longevity·Suk-Yee LiAmy C Y Lo
Oct 4, 2005·The Journal of Clinical Investigation·Lisa Bouchier-HayesDonald D Newmeyer
Jun 10, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Tetsuji Miura, Takayuki Miki
Nov 17, 2007·Environmental Health Perspectives·Thomas C LongBellina Veronesi
May 30, 2008·PloS One·David DupretPier Vincenzo Piazza
Aug 18, 2009·Gynécologie, obstétrique & fertilité·I BoumelaA Aouacheria
Aug 31, 2004·Journal of Cellular Physiology·Laurent DejeanFrancesc Villarroya
Nov 9, 2004·The Anatomical Record. Part A, Discoveries in Molecular, Cellular, and Evolutionary Biology·Antonio SessoJoyce T Kawakami
Oct 5, 2010·The Journal of Thoracic and Cardiovascular Surgery·Chung Ho LeungChristopher A Caldarone
Aug 17, 2010·Mitochondrion·Lina Ghibelli, Marc Diederich
Jul 6, 2010·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Aliny Pereira de LimaElisângela de Paula Silveira Lacerda
Mar 17, 2009·Journal of Molecular and Cellular Cardiology·D KatragaddaJ M Seubert
Mar 1, 2016·Biochimica Et Biophysica Acta·Nicolas Tajeddine
Jul 25, 2006·Clinical Genitourinary Cancer·Anirban P MitraRichard J Cote

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

American Journal of Physiology. Cell Physiology
Liang GuoKathleen W Kinnally
The Journal of Biological Chemistry
Gilles GuihardFrançois Marie Vallette
The Biochemical Journal
Michela Capano, Martin Crompton
© 2022 Meta ULC. All rights reserved