Regulation and pharmacology of the mitochondrial permeability transition pore

Zorov, Dmitry B.; Juhaszova, Magdalena; Yaniv, Yael; Nuss, Hanne; Wang, Su; Sollott, Steven J.

doi:10.1093/cvr/cvp151

Cited by 214 publications

(194 citation statements)

References 141 publications

(177 reference statements)

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“…It is at least prudent to consider that the composition and/or regulation of the mitochondrial PTP exhibits tissue-or even cell-specific differences, as it has been suggested elsewhere (44,45). …”

Section: Discussionmentioning

confidence: 99%

Complex Contribution of Cyclophilin D to Ca2+-induced Permeability Transition in Brain Mitochondria, with Relation to the Bioenergetic State

Dóczi

Turiák

Vajda

et al. 2011

Journal of Biological Chemistry

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Cyclophilin D (cypD)-deficient mice exhibit resistance to focal cerebral ischemia and to necrotic but not apoptotic stimuli. To address this disparity, we investigated isolated brain and in situ neuronal and astrocytic mitochondria from cypDdeficient and wild-type mice. Isolated mitochondria were challenged by high Ca 2؉ , and the effects of substrates and respiratory chain inhibitors were evaluated on permeability transition pore opening by light scatter. In situ neuronal and astrocytic mitochondria were visualized by mito-DsRed2 targeting and challenged by calcimycin, and the effects of glucose, NaCN, and an uncoupler were evaluated by measuring mitochondrial volume. In isolated mitochondria, Ca 2؉ caused a large cypDdependent change in light scatter in the absence of substrates that was insensitive to Ruthenium red or Ru360. Uniporter inhibitors only partially affected the entry of free Ca 2؉ in the matrix. Inhibition of complex III/IV negated the effect of substrates, but inhibition of complex I was protective. Mitochondria within neurons and astrocytes exhibited cypD-independent swelling that was dramatically hastened when NaCN and 2-deoxyglucose were present in a glucose-free medium during calcimycin treatment. In the presence of an uncoupler, cypD-deficient astrocytic mitochondria performed better than wild-type mitochondria, whereas the opposite was observed in neurons. Neuronal mitochondria were examined further during glutamate-induced delayed Ca 2؉ deregulation. CypD-knock-out mitochondria exhibited an absence or a delay in the onset of mitochondrial swelling after glutamate application. Apparently, some conditions involving deenergization render cypD an important modulator of PTP in the brain. These findings could explain why absence of cypD protects against necrotic (deenergized mitochondria), but not apoptotic (energized mitochondria) stimuli.

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Section: Discussionmentioning

confidence: 99%

Complex Contribution of Cyclophilin D to Ca2+-induced Permeability Transition in Brain Mitochondria, with Relation to the Bioenergetic State

Dóczi

Turiák

Vajda

et al. 2011

Journal of Biological Chemistry

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“…It is clear that mitochondrial permeability transition (MPT) pore formation is characterized by the loss of mitochondrial transmembrane potential (MTP) and plays a key role in determining whether the cell lives or dies (Zorov et al, 2009). However, in terpinen-4-ol-treated HL-60 cells, cytochrome c release was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

Banjerdpongchai¹,

Khaw-on²

2013

Asian Pacific Journal of Cancer Prevention

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“…However, recent studies with mitochondria from knockout mice have suggested that Cyp-D has more of a regulatory role in mPTP opening. In contrast, VDAC appears dispensable for pore formation, and at this time there is no compelling evidence that VDAC serves a regulatory role either [27].…”

Section: Mitochondrial Permeability Transition Porementioning

confidence: 92%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

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Regulation and pharmacology of the mitochondrial permeability transition pore

Abstract: The 'mitochondrial permeability transition', characterized by a sudden induced change of the inner mitochondrial membrane permeability for water as well as for small substances ( Show more

Cited by 214 publications

References 141 publications

Complex Contribution of Cyclophilin D to Ca2+-induced Permeability Transition in Brain Mitochondria, with Relation to the Bioenergetic State

Complex Contribution of Cyclophilin D to Ca2+-induced Permeability Transition in Brain Mitochondria, with Relation to the Bioenergetic State

Terpinen-4-ol Induces Autophagic and Apoptotic Cell Death in Human Leukemic HL-60 Cells

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

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