Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during stress-induced apoptosis

Tomasello, Marianna Flora; Messina, Angela; Lartigue, Lydia; Schembri, Laura; Médina, Chantal; Reina, Simona; Thoraval, Didier; Crouzet, Marc; Ichas, François; Pinto, Vito De; Giorgi, Francesca De

doi:10.1038/cr.2009.98

Cited by 124 publications

(98 citation statements)

References 69 publications

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“…36 Recently, it was shown, at the single cell level that silencing of VDAC1 expression by siRNA results in the inhibition of mitochondrial permeability transition, as induced by selenite. 37 These observations do not contradict our finding that VDAC1 silencing leads to cell growth attenuation, since when employing VDAC silencing therapeutic tools alone, the outcome effect could be cell growth inhibition, per se.…”

Section: Discussioncontrasting

confidence: 52%

“…Indeed, several other studies employing siRNA-based silencing of VDAC1 expression have revealed that VDAC is required for apoptosis, as induced by various stimuli. [35][36][37] It has been shown that VDAC1 silencing by siRNA prevented cisplatin-induced apoptosis and Bax activation in non-small cell lung cancer cells. 35 Another study showed that VDAC1 silencing by siRNA attenuated endostatin-induced apoptosis, while VDAC1 overexpression enhanced the sensitivity of endothelial cells towards endostatin.…”

Section: Discussionmentioning

confidence: 99%

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Downregulation of voltage-dependent anion channel-1 expression by RNA interference prevents cancer cell growth in vivo

Koren¹,

Raviv²,

Shoshan‐Barmatz³

2010

Cancer Biology & Therapy

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Section: Discussioncontrasting

confidence: 52%

Section: Discussionmentioning

confidence: 99%

Downregulation of voltage-dependent anion channel-1 expression by RNA interference prevents cancer cell growth in vivo

Koren¹,

Raviv²,

Shoshan‐Barmatz³

2010

Cancer Biology & Therapy

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“…Apoptosis was characterized by the mitochondrial proteins cytochrome c and AIF, which are commonly released following ROS-induced increases in mitochondrial outer membrane permeability (34,35). Inhibiting fatty acid oxidation by blocking CPT1 with etomoxir resulted in ROS-dependent death of glioma cells caused by reduced concentrations of intracellular antioxidants attributed to decreased NADPH (26).…”

Section: Discussionmentioning

confidence: 99%

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death

et al. 2015

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Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function. Cancer Res; 75(12); 2478-88. Ó2015 AACR.

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“…Indeed, VDACs have been shown to interact with cytoskeletal elements such as actin and tubulin, 4,5 metabolic enzymes, 6 Bcl2-family members including Bak, 7 Bad, 8 tBid 9 and Bcl-xL 10 or other channels such as ANT, 11 or the IP 3 R. 12,13 This scenario is further complicated by evidence showing that VDAC contribution to cell death can be isoform and stimulus dependent: VDAC1 acts predominantly as a pro-apoptotic protein [14][15][16][17] whereas VDAC2 protects from a number of apoptosis inducers, 18 but concurrently appears to be necessary for tBid-mediated cell-death. 9 However, these different effects are not supported by the apparent redundancy in the electrophysiological properties of the isoforms.…”

mentioning

confidence: 99%

VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria

et al. 2011

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Voltage-dependent anion channels (VDACs) are expressed in three isoforms, with common channeling properties and different roles in cell survival. We show that VDAC1 silencing potentiates apoptotic challenges, whereas VDAC2 has the opposite effect. Although all three VDAC isoforms are equivalent in allowing mitochondrial Ca 2 þ loading upon agonist stimulation, VDAC1 silencing selectively impairs the transfer of the low-amplitude apoptotic Ca 2 þ signals. Co-immunoprecipitation experiments show that VDAC1, but not VDAC2 and VDAC3, forms complexes with IP 3 receptors, an interaction that is further strengthened by apoptotic stimuli. These data highlight a non-redundant molecular route for transferring Ca 2 þ signals to mitochondria in apoptosis.

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Outer membrane VDAC1 controls permeability transition of the inner mitochondrial membrane in cellulo during stress-induced apoptosis

Cited by 124 publications

References 69 publications

Downregulation of voltage-dependent anion channel-1 expression by RNA interference prevents cancer cell growth in vivo

Downregulation of voltage-dependent anion channel-1 expression by RNA interference prevents cancer cell growth in vivo

Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death

VDAC1 selectively transfers apoptotic Ca2+ signals to mitochondria

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