Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity

Bertholet, Ambre M.; Delerue, Thomas; Millet, Aurélie; Moulis, Manon; David, Claudine; Daloyau, Marlène; Arnauné-Pelloquin, Laetitia; Davezac, Noélie; Mils, Valérie; Miquel, Marie‐Christine; Rojo, Manuel; Bélenguer, Pascale

doi:10.1016/j.nbd.2015.10.011

Cited by 292 publications

(195 citation statements)

References 302 publications

Supporting

Mentioning

193

Contrasting

Unclassified

Order By: Relevance

“…It has been proven that increased Drp1/p-Drp1(S616) levels enhance mitochondrial fragmentation [34] and that excessive fragmentation of mitochondria is implicated in the synaptic damage observed in neurodegenerative diseases [13, 35] and T2DM [15, 16]. Although both T1DM and T2DM have been associated with reduced performance in multiple domains of cognitive function and with abnormal brain structure and function in magnetic resonance imaging (MRI) studies, important differences exist.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Zhou

Lian

Zhang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Mitochondrial perturbation is a well-established cause of cognitive decline, but as yet it is unclear how mitochondria-associated neuronal abnormalities in type 1 diabetic (T1DM) brain contribute to cognitive decline. Methods: The streptozotocin (STZ)-induced mouse model of T1DM was used. The Morris water maze test was applied to assess the effect of T1DM on learning and memory. We detected changes in mitochondrial morphology, function and dynamics. Furthermore, we employed metabolomic analysis to reveal the underlying mechanisms of mitochondrial perturbation which contribute to cognitive decline. Results: Our results show that T1DM impairs mitochondrial dynamics, morphology and function in neurons, associated with a decline in cognitive ability. Metabolomic analyses revealed that T1DM mainly affects metabolic pathways involved in mitochondrial energy failure and impairs the antioxidative system. Conclusion: These results lay the basis for understanding the underlying mitochondria-associated causes of T1DM-associated cognitive decline and may provide a potential treatment strategy for this condition in future.

show abstract

Section: Discussionmentioning

confidence: 99%

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Zhou

Lian

Zhang

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…This import signal directs Opa1 protein to mitochondria, where it is removed by proteolytic cleavage, which generates the inner membrane-anchored long isoform of Opa1, L-Opa1 (Bertholet et al, 2016; Song et al, 2007). Under steady-state conditions, a fraction of the L-Opa1 pool is further proteolytically cleaved at two sites S1 and S2 to generate a short isoform lacking the transmembrane domain, S-Opa1 (Bertholet et al, 2016; Ishihara et al, 2006).…”

Section: Cellular Machinery Of Mitochondrial Fusionmentioning

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

“…More specifically, mitochondria are of vital importance for neuronal synaptic development, plasticity, and loss (Flippo & Strack, 2017). During cell proliferation and development, mitochondria provide sufficient energy and undergo continual fission and fusion events mediated by GTPases, such as dynamin‐like protein 1 (DLP1) for fission and mitofusins (MFNs) for fusion (Bertholet et al ., 2016). Fis1 and DLP1 are both mitochondrial fission proteins but Fis1 primarily plays a role in transporting DLP1 from cytoplasm to mitochondrial surface before the oligomerized DLP1 forms a ring which constricts the organelle and eventually leads to fission (Yoon et al ., 2003).…”

Section: Introductionmentioning

confidence: 99%

“…Because of the vital role of mitochondria in neurons, deficient mitochondrial dynamics are believed to be a culprit for neurodegenerative diseases (Bertholet et al ., 2016; Li et al ., 2016; Yang et al ., 2016). In Alzheimer's disease (AD) brains, increased level of mitochondrial DLP1 is a primary factor for altered balance in mitochondrial division and fusion, which is likely an important mechanism leading to synaptic loss and neural dysfunction (Wang et al ., 2009).…”

Section: Introductionmentioning

confidence: 99%

DLP1‐dependent mitochondrial fragmentation and redistribution mediate prion‐associated mitochondrial dysfunction and neuronal death

Wang

et al. 2017

Aging Cell

View full text Add to dashboard Cite

SummaryMitochondrial malfunction is a universal and critical step in the pathogenesis of many neurodegenerative diseases including prion diseases. Dynamin‐like protein 1 (DLP1) is one of the key regulators of mitochondrial fission. In this study, we investigated the role of DLP1 in mitochondrial fragmentation and dysfunction in neurons using in vitro and in vivo prion disease models. Mitochondria became fragmented and redistributed from axons to soma, correlated with increased mitochondrial DLP1 expression in murine primary neurons (N2a cells) treated with the prion peptide PrP106–126 in vitro as well as in prion strain‐infected hamster brain in vivo. Suppression of DLP1 expression by DPL1 RNAi inhibited prion‐induced mitochondrial fragmentation and dysfunction (measured by ADP/ATP ratio, mitochondrial membrane potential, and mitochondrial integrity). We also demonstrated that DLP1 RNAi is neuroprotective against prion peptide in N2a cells as shown by improved cell viability and decreased apoptosis markers, caspase 3 induced by PrP106–126. On the contrary, overexpression of DLP1 exacerbated mitochondrial dysfunction and cell death. Moreover, inhibition of DLP1 expression ameliorated PrP106–126‐induced neurite loss and synaptic abnormalities (i.e., loss of dendritic spine and PSD‐95, a postsynaptic scaffolding protein as a marker of synaptic plasticity) in primary neurons, suggesting that altered DLP1 expression and mitochondrial fragmentation are upstream events that mediate PrP106–126‐induced neuron loss and degeneration. Our findings suggest that DLP1‐dependent mitochondrial fragmentation and redistribution plays a pivotal role in PrPS c‐associated mitochondria dysfunction and neuron apoptosis. Inhibition of DLP1 may be a novel and effective strategy in the prevention and treatment of prion diseases.

show abstract

Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity

Cited by 292 publications

References 302 publications

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

Mitochondrial Perturbation Contributing to Cognitive Decline in Streptozotocin-Induced Type 1 Diabetic Rats

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

DLP1‐dependent mitochondrial fragmentation and redistribution mediate prion‐associated mitochondrial dysfunction and neuronal death

Contact Info

Product

Resources

About