Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane

Lucken-Ardjomande, Safa; Martinou, Jean‐Claude

doi:10.1016/j.crvi.2005.05.002

Cited by 89 publications

(70 citation statements)

References 126 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These killer proteases target many vital proteins, committing the cell to death (Fischer et al, 2003). Mitochondrial membrane permeabilization is regulated by members of the Bcl2 family (Lucken-Ardjomande and Martinou, 2005b). These proteins contain at least one of the four conserved regions called Bcl2-Homology domains (BH1-BH4).…”

Section: Mitochondrial Membrane Permeabilizationmentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

View full text Add to dashboard Cite

Mitochondria are key players in several cellular functions including growth, division, energy metabolism, and apoptosis. The mitochondrial network undergoes constant remodelling and these morphological changes are of direct relevance for the role of this organelle in cell physiology. Mitochondrial dysfunction contributes to a number of human disorders and may aid cancer progression. Here, we summarize the recent contributions made in the field of mitochondrial dynamics and discuss their impact on our understanding of cell function and tumorigenesis.

show abstract

Section: Mitochondrial Membrane Permeabilizationmentioning

confidence: 99%

Mitochondria and cancer: is there a morphological connection?

2006

View full text Add to dashboard Cite

show abstract

“…8 As antiapoptotic members of the Bcl-2 family prevent the increase in membrane permeability and protect cells from various death insults, it has been assumed that Bcl-2 family members primarily regulate mitochondrial integrity, and thus the crucial commitment step in many apoptotic routes. 9 However, in the recent years also the other potential sites of Bcl-2 action regained interest, for at least two reasons. The first is that mitochondrial apoptotic involvement could depend on signals that originate from other cell compartments.…”

Section: Introductionmentioning

confidence: 99%

Bcl-2 and Ca2+ homeostasis in the endoplasmic reticulum

2006

View full text Add to dashboard Cite

Recent data have revealed an unexpected role of Bcl-2 in modulating the steady-state levels and agonist-dependent fluxes of Ca 2 þ ions. Direct monitoring of endoplasmic reticulum (ER) Ca 2 þ concentration with recombinant probes reveals a lower state of filling in Bcl-2-overexpressing cells and a higher leak rate from the organelle. The broader set of indirect data using cytosolic probes reveals a more complex scenario, as in many cases no difference was detected in the Ca 2 þ content of the intracellular pools. At the same time, Ca 2 þ signals have been shown to affect important checkpoints of the apoptotic process, such as mitochondria, thus tuning the sensitivity of cells to various challenges. In this contribution, we will review (i) the data on the effect of Bcl-2 on [Ca 2 þ ] er , (ii) the functional significance of the Ca 2 þ -signalling alteration and (iii) the current insight into the possible mechanisms of this effect.

show abstract

“…12 Mitochondria have a central role as the garden of cell death, which regulates mitochondrial membrane potential (DeltaPsim) and mitochondrial outer membrane permeabilization (MOMP). 13,14 Chemotherapeutic druginduced decrease in DeltaPsim leads to an increase in MOMP, resulting in the release of proapoptotic small molecules such as cytochrome c, second mitochondriaderived activator of caspase/direct inhibitor of apoptosisbinding protein with low pl (Smac/DIABLO) and apoptosis-inducing factor (AIF) through permeability transition pores in caspase-dependent and -independent pathways. 15,16 Chemotherapeutic drug-induced MOMP promotes Bax/Bak oligomerization and their translocation to mitochondrial membranes, which induces the release of proapoptotic molecules from the mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy

et al. 2006

View full text Add to dashboard Cite

Bcl-2 is an oncoprotein that plays a critical role in inhibiting apoptotic cell death in the mitochondria-dependent pathway in cancer chemotherapy. As a strategy for blocking Bcl-2 for enhancement of the chemotherapeutic effect, antisense Bcl-2 (AS Bcl-2; G3139, oblimersen sodium, Genasense) has shown promise, and there are several ongoing clinical studies with hematological malignancies as well as solid tumors. Although several preclinical and clinical studies have shown the therapeutic efficacy of Bcl-2 in combination with an anticancer drug as a chemosensitizer, in clinical trials the downregulation of Bcl-2 has not been observed with a high frequency in tumor cells. Nevertheless, previous studies showed nonantisense effects such as production of reactive oxygen species and immunostimulatory action through cytosine-phosphate-guanosine-motif in the antisense oligodeoxynucleotides. Further, Bcl-2 is able to inhibit Beclin 1-dependent autophagic cell death, which is a nonapoptotic cell death. The current status and future directions of AS Bcl-2 and the potential mechanisms for multiple roles that Bcl-2 has in cancer therapy are reviewed.

show abstract

Regulation of Bcl-2 proteins and of the permeability of the outer mitochondrial membrane

Cited by 89 publications

References 126 publications

Mitochondria and cancer: is there a morphological connection?

Mitochondria and cancer: is there a morphological connection?

Bcl-2 and Ca2+ homeostasis in the endoplasmic reticulum

Antisense and nonantisense effects of antisense Bcl-2 on multiple roles of Bcl-2 as a chemosensitizer in cancer therapy

Contact Info

Product

Resources

About