scholarly journals Mitochondrial morphology transitions and functions: implications for retrograde signaling?

2013 ◽  
Vol 304 (6) ◽  
pp. R393-R406 ◽  
Author(s):  
Martin Picard ◽  
Orian S. Shirihai ◽  
Benoit J. Gentil ◽  
Yan Burelle
Keyword(s):  
Cell Function ◽  
Mitochondrial Permeability Transition ◽  
Mitochondrial Dynamics ◽  
Permeability Transition ◽  
Retrograde Signaling ◽  
Mitochondrial Morphology ◽  
Transport Chain ◽  
Dynamic Interface ◽  
Morphological Transitions ◽  
Species Production

In response to cellular and environmental stresses, mitochondria undergo morphology transitions regulated by dynamic processes of membrane fusion and fission. These events of mitochondrial dynamics are central regulators of cellular activity, but the mechanisms linking mitochondrial shape to cell function remain unclear. One possibility evaluated in this review is that mitochondrial morphological transitions (from elongated to fragmented, and vice-versa) directly modify canonical aspects of the organelle's function, including susceptibility to mitochondrial permeability transition, respiratory properties of the electron transport chain, and reactive oxygen species production. Because outputs derived from mitochondrial metabolism are linked to defined cellular signaling pathways, fusion/fission morphology transitions could regulate mitochondrial function and retrograde signaling. This is hypothesized to provide a dynamic interface between the cell, its genome, and the fluctuating metabolic environment.

scholarly journals Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia-reperfusion injury: implications for pharmacological cardioprotection

2018 ◽  
Vol 315 (5) ◽  
pp. H1341-H1352 ◽  
Author(s):  
Giuseppe Paradies ◽  
Valeria Paradies ◽  
Francesca Maria Ruggiero ◽  
Giuseppe Petrosillo
Keyword(s):  
Myocardial Ischemia ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Morphology ◽  
Myocardial Ischemia Reperfusion

Mitochondrial dysfunction plays a central role in myocardial ischemia-reperfusion (I/R) injury. Increased reactive oxygen species production, impaired electron transport chain activity, aberrant mitochondrial dynamics, Ca2+ overload, and opening of the mitochondrial permeability transition pore have been proposed as major contributory factors to mitochondrial dysfunction during myocardial I/R injury. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a pivotal role in multiple mitochondrial bioenergetic processes, including respiration and energy conversion, in mitochondrial morphology and dynamics as well as in several steps of the apoptotic process. Changes in CL levels, species composition, and degree of oxidation may have deleterious consequences for mitochondrial function with important implications in a variety of pathophysiological conditions, including myocardial I/R injury. In this review, we focus on the role played by CL alterations in mitochondrial dysfunction in myocardial I/R injury. Pharmacological strategies to prevent myocardial injury during I/R targeting mitochondrial CL are also examined.

scholarly journals The novel cyclophilin-D-interacting protein FASTKD1 protects cells against oxidative stress-induced cell death

2019 ◽  
Vol 317 (3) ◽  
pp. C584-C599
Author(s):  
Kurt D. Marshall ◽  
Paula J. Klutho ◽  
Lihui Song ◽  
Maike Krenz ◽  
Christopher P. Baines
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Kinase Domain ◽  
Protective Role ◽  
Mitochondrial Morphology ◽  
Cyclophilin D ◽  
Interacting Protein ◽  
Mitochondrial Homeostasis

Opening of the mitochondrial permeability transition (MPT) pore leads to necrotic cell death. Excluding cyclophilin D (CypD), the makeup of the MPT pore remains conjecture. The purpose of these experiments was to identify novel MPT modulators by analyzing proteins that associate with CypD. We identified Fas-activated serine/threonine phosphoprotein kinase domain-containing protein 1 (FASTKD1) as a novel CypD interactor. Overexpression of FASTKD1 protected mouse embryonic fibroblasts (MEFs) against oxidative stress-induced reactive oxygen species (ROS) production and cell death, whereas depletion of FASTKD1 sensitized them. However, manipulation of FASTKD1 levels had no effect on MPT responsiveness, Ca2+-induced cell death, or antioxidant capacity. Moreover, elevated FASTKD1 levels still protected against oxidative stress in CypD-deficient MEFs. FASTKD1 overexpression decreased Complex-I-dependent respiration and ΔΨm in MEFs, effects that were abrogated in CypD-null cells. Additionally, overexpression of FASTKD1 in MEFs induced mitochondrial fragmentation independent of CypD, activation of Drp1, and inhibition of autophagy/mitophagy, whereas knockdown of FASTKD1 had the opposite effect. Manipulation of FASTKD1 expression also modified oxidative stress-induced caspase-3 cleavage yet did not alter apoptotic death. Finally, the effects of FASTKD1 overexpression on oxidative stress-induced cell death and mitochondrial morphology were recapitulated in cultured cardiac myocytes. Together, these data indicate that FASTKD1 supports mitochondrial homeostasis and plays a critical protective role against oxidant-induced death.

scholarly journals Cell death during ischemia: relationship to mitochondrial depolarization and ROS generation

2003 ◽  
Vol 284 (2) ◽  
pp. H549-H558 ◽  
Author(s):  
Jacques Levraut ◽  
Hirotaro Iwase ◽  
Z.-H. Shao ◽  
Terry L. Vanden Hoek ◽  
Paul T. Schumacker
Keyword(s):  
Cell Death ◽  
Mitochondrial Permeability Transition ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Permeability Transition ◽  
Ros Generation ◽  
Ischemia And Reperfusion ◽  
Mitochondrial Depolarization ◽  
Sytox Green ◽  
Transport Chain

Ischemia-reperfusion injury induces cell death, but the responsible mechanisms are not understood. This study examined mitochondrial depolarization and cell death during ischemia and reperfusion. Contracting cardiomyocytes were subjected to 60-min ischemia followed by 3-h reperfusion. Mitochondrial membrane potential (ΔΨm) was assessed with tetramethylrhodamine methyl ester. During ischemia, ΔΨm decreased to 24 ± 5.5% of baseline, but no recovery was evident during reperfusion. Cell death assessed by Sytox Green was minimal during ischemia but averaged 66 ± 7% after 3-h reperfusion. Cyclosporin A, an inhibitor of mitochondrial permeability transition, was not protective. However, pharmacological antioxidants attenuated the fall in ΔΨm during ischemia and cell death after reperfusion and decreased lipid peroxidation as assessed with C11-BODIPY. Cell death was also attenuated when residual O2 was scavenged from the perfusate, creating anoxic ischemia. These results suggested that reactive oxygen species (ROS) were important for the decrease in ΔΨm during ischemia. Finally, 143B-ρ0 osteosarcoma cells lacking a mitochondrial electron transport chain failed to demonstrate a depletion of ΔΨm during ischemia and were significantly protected against cell death during reperfusion. Collectively, these studies identify a central role for mitochondrial ROS generation during ischemia in the mitochondrial depolarization and subsequent cell death induced by ischemia and reperfusion in this model.

scholarly journals Role of Calcium and Mitochondria in MeHg-Mediated Cytotoxicity

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Daniel Roos ◽  
Rodrigo Seeger ◽  
Robson Puntel ◽  
Nilda Vargas Barbosa
Keyword(s):  
Mitochondrial Permeability Transition ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Mitochondrial Dysfunctions ◽  
Mptp Opening ◽  
Molecular Events ◽  
Chain Complexes ◽  
Transport Chain ◽  
Intracellular Ca

Methylmercury (MeHg) mediated cytotoxicity is associated with loss of intracellular calcium (Ca2+) homeostasis. The imbalance in Ca2+physiology is believed to be associated with dysregulation of Ca2+intracellular stores and/or increased permeability of the biomembranes to this ion. In this paper we summarize the contribution of glutamate dyshomeostasis in intracellular Ca2+overload and highlight the mitochondrial dysfunctions induced by MeHg via Ca2+overload. Mitochondrial disturbances elicited by Ca2+may involve several molecular events (i.e., alterations in the activity of the mitochondrial electron transport chain complexes, mitochondrial proton gradient dissipation, mitochondrial permeability transition pore (MPTP) opening, thiol depletion, failure of energy metabolism, reactive oxygen species overproduction) that could culminate in cell death. Here we will focus on the role of oxidative stress in these phenomena. Additionally, possible antioxidant therapies that could be effective in the treatment of MeHg intoxication are briefly discussed.

Sign in / Sign up

Export Citation Format

Share Document