DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress

Björn, Oettinghaus; D’Alonzo, Donato; Barbieri, Elisa; Restelli, Lisa Michelle; Savoia, Claudia; Licci, Maria; Tolnay, Markus; Frank, Stephan; Scorrano, Luca

doi:10.1016/j.bbabio.2016.03.016

Cited by 60 publications

(45 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DRP1 behavior is thus similar to pro-apoptotic BAX, which is recruited to the outer mitochondrial membrane during apoptosis and oligomerizes into foci that are functionally linked to MOMP. Indeed, DRP1 has been found in foci with BAX on mitochondria during apoptosis [112–114], however, DRP1-mediated cell death may not necessarily require BAX and BAK in other cell types [115, 116]. MFN2 similarly behaves like DRP1 under apoptotic conditions and has been found in foci with BAX [112, 117].…”

Section: The Role Of Er In Mitochondrial Dynamicsmentioning

confidence: 99%

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Bhat

Chaudhary

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

105

View full text Add to dashboard Cite

Abrogation of endoplasmic reticulum (ER) protein folding triggered by exogenous or endogenous factors, stimulates a cellular stress response, termed ER stress. ER stress reestablishes ER homeostasis through integrated signaling termed the ER-unfolded protein response (UPRER). In the presence of severe toxic or prolonged ER stress, the pro-survival function of UPRER is transformed into a lethal signal transmitted to and executed through mitochondria. Mitochondria are key for both apoptotic and autophagic cell death. Thus ER is vital in sensing and coordinating stress pathways to maintain overall physiological homeostasis. However, this function is deregulated in cancer, resulting in resistance to apoptosis induction in response to various stressors including therapeutic agents. Here we review the connections between ER stress and mitochondrial apoptosis, describing potential cancer therapeutic targets.

show abstract

Section: The Role Of Er In Mitochondrial Dynamicsmentioning

confidence: 99%

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Bhat

Chaudhary

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

105

View full text Add to dashboard Cite

show abstract

“…Oncogenic Ras may promote tumorigenesis in part by stimulating mitochondrial fission dependent on ERK phosphorylation on Drp1 Ser616, consistent with high levels of phospho-S616 in pancreatic cancer (Kashatus et al, 2015), and possibly also glioblastoma (Xie et al, 2015). However, Drp1-dependent fission induced by some death stimuli can induce MOMP independently of Bax, Bak or other apoptosis factors, implying the involvement of other factors (Oettinghaus et al, 2016). Drp1 inhibitors are being developed as potential therapeutics to suppress neurodegeneration.…”

Section: Cellular Machinery Of Mitochondrial Fissionmentioning

confidence: 99%

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins

Aouacheria

Baghdiguian

Lamb

et al. 2017

Neurochemistry International

View full text Add to dashboard Cite

The morphology of a population of mitochondria is the result of several interacting dynamical phenomena, including fission, fusion, movement, elimination and biogenesis. Each of these phenomena is controlled by underlying molecular machinery, and when defective can cause disease. New understanding of the relationships between form and function of mitochondria in health and disease is beginning to be unraveled on several fronts. Studies in mammals and model organisms have revealed that mitochondrial morphology, dynamics and function appear to be subject to regulation by the same proteins that regulate apoptotic cell death. One protein family that influences mitochondrial dynamics in both healthy and dying cells is the Bcl-2 protein family. Connecting mitochondrial dynamics with life-death pathway forks may arise from the intersection of Bcl-2 family proteins with the proteins and lipids that determine mitochondrial shape and function. Bcl-2 family proteins also have multifaceted influences on cells and mitochondria, including calcium handling, autophagy and energetics, as well as the subcellular localization of mitochondrial organelles to neuronal synapses. The remarkable range of physical or functional interactions by Bcl-2 family proteins is challenging to assimilate into a cohesive understanding. Most of their effects may be distinct from their direct roles in apoptotic cell death and are particularly apparent in the nervous system. Dual roles in mitochondrial dynamics and cell death extend beyond BCL-2 family proteins. In this review, we discuss many processes that govern mitochondrial structure and function in health and disease, and how Bcl-2 family proteins integrate into some of these processes.

show abstract

“…For example, during nutrient starvation, functional mitochondria undergo fusion and elongation, protecting them from degradation (58), while mitochondria with low Δψ m are selectively targeted for autophagy via PINK1/Parkin signaling (59). Similarly, DRP1-mediated mitochondrial fission is an integral component of apoptotic pathways (60), while OPA1 interacts with SIRT3 as part of cellular stress response signaling (61). Collectively, mitochondrial structural dynamics are critical to the organelle’s role in both bioenergetics and crucial cell-wide signaling events, directly impacting the survival or death of the cell.…”

Section: Integration Of Mtdna Into the Organellar Networkmentioning

confidence: 99%

The little big genome the organization of mitochondrial DNA

Garcia¹,

Jones²,

Ramos

et al. 2017

Front Biosci

View full text Add to dashboard Cite

The small (16,569 base pair) human mitochondrial genome plays a significant role in cell metabolism and homeostasis. Mitochondrial DNA (mtDNA) contributes to the generation of complexes which are essential to oxidative phosphorylation (OXPHOS). As such, mtDNA is directly integrated into mitochondrial biogenesis and signaling and regulates mitochondrial metabolism in concert with nuclear-encoded mitochondrial factors. Mitochondria are a highly dynamic, pleiomorphic network that undergoes fission and fusion events. Within this network, mtDNAs are packaged into structures called nucleoids which are actively distributed in discrete foci within the network. This sensitive organelle is frequently disrupted by insults such as oxidants and inflammatory cytokines, and undergoes genomic damage with double- and single-strand breaks that impair its function. Collectively, mtDNA is emerging as a highly sensitive indicator of cellular stress, which is directly integrated into the mitochondrial network as a contributor of a wide range of critical signaling pathways.

show abstract

DRP1-dependent apoptotic mitochondrial fission occurs independently of BAX, BAK and APAF1 to amplify cell death by BID and oxidative stress

Cited by 60 publications

References 57 publications

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Endoplasmic reticulum-mediated unfolded protein response and mitochondrial apoptosis in cancer

Connecting mitochondrial dynamics and life-or-death events via Bcl-2 family proteins

The little big genome the organization of mitochondrial DNA

Contact Info

Product

Resources

About