Mitochondrial fission/fusion dynamics and apoptosis

Sheridan, Clare; Martin, Séamus J.

doi:10.1016/j.mito.2010.08.005

Cited by 199 publications

(161 citation statements)

References 112 publications

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“…The mitochondria are most dynamic organelles frequently involved in the process of fusion and fission forming an interconnecting tubular network and also individual entity (49). However, during apoptosis, mitochondria undergo fragmentation, which results in enhanced accumulation of smaller mitochondria (49). We have observed that Drp-1 significantly involved in regulating the mitochondrial shape, their fragmentation, and also functions.…”

Section: Discussionmentioning

confidence: 87%

“…The impaired mitochondrial dynamics was associated with the increase in the levels of Drp-1 with insignificant changes in other mitochondrial dynamin-related proteins. The mitochondria are most dynamic organelles frequently involved in the process of fusion and fission forming an interconnecting tubular network and also individual entity (49). However, during apoptosis, mitochondria undergo fragmentation, which results in enhanced accumulation of smaller mitochondria (49).…”

Section: Discussionmentioning

confidence: 99%

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Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

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The regulatory dynamics of mitochondria comprises well orchestrated distribution and mitochondrial turnover to maintain the mitochondrial circuitry and homeostasis inside the cells. Several pieces of evidence suggested impaired mitochondrial dynamics and its association with the pathogenesis of neurodegenerative disorders. We found that chronic exposure of synthetic xenoestrogen bisphenol A (BPA), a component of consumer plastic products, impaired autophagy-mediated mitochondrial turnover, leading to increased oxidative stress, mitochondrial fragmentation, and apoptosis in hippocampal neural stem cells (NSCs). It also inhibited hippocampal derived NSC proliferation and differentiation, as evident by the decreased number of BrdU-and ␤-III tubulin-positive cells. All these effects were reversed by the inhibition of oxidative stress using N-acetyl cysteine. BPA up-regulated the levels of Drp-1 (dynamin-related protein 1) and enhanced its mitochondrial translocation, with no effect on Fis-1, Mfn-1, Mfn-2, and Opa-1 in vitro and in the hippocampus. Moreover, transmission electron microscopy studies suggested increased mitochondrial fission and accumulation of fragmented mitochondria and decreased elongated mitochondria in the hippocampus of the rat brain. Impaired mitochondrial dynamics by BPA resulted in increased reactive oxygen species and malondialdehyde levels, disruption of mitochondrial membrane potential, and ATP decline. Pharmacological (Mdivi-1) and genetic (Drp-1siRNA) inhibition of Drp-1 reversed BPA-induced mitochondrial dysfunctions, fragmentation, and apoptosis. Interestingly, BPAmediated inhibitory effects on NSC proliferation and neuronal differentiations were also mitigated by Drp-1 inhibition. On the other hand, Drp-1 inhibition blocked BPA-mediated Drp-1 translocation, leading to decreased apoptosis of NSC. Overall, our studies implicate Drp-1 as a potential therapeutic target against BPA-mediated impaired mitochondrial dynamics and neurodegeneration in the hippocampus.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Dynamin-related Protein 1 Inhibition Mitigates Bisphenol A-mediated Alterations in Mitochondrial Dynamics and Neural Stem Cell Proliferation and Differentiation

Agarwal

Yadav

Tiwari

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Neurons are especially sensitive to imbalances in the axonal mitochondrial transport process as both energy supply and calcium handling are vital at the synapse [8]. At the other extreme, excessive stress generally results in mitochondrial fragmentation and formation of small, punctate mitochondria and ultimately, apoptosis if the cell is too damaged [89,90].…”

Section: Hormesis In Action-mitochondrial Networkmentioning

confidence: 99%

The Hormesis of Thinking: A Deeper Quantum Thermodynamic Perspective?

Nunn¹,

Guy²,

Bell³

2017

Int J Neurorehabilitation Eng

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We are able to read this because of quantum and thermodynamic principles that via an inorganic proton gradient, possibly generated 4.2 billion years ago, gave rise to a system that has an awareness of time and space by using energy to integrate information. Life can be described as a dissipative system driven by an energy gradient that uses information to positively reinforce its self-sustaining structure, which in turn increases its non-linear decisional capacity. Key in the evolution of life has been stress coupled to natural selection, which usually meant an increased demand for energy. As hormesis describes the adaptive response to stress, we propose that hormesis embraces not only the evolution of life, but that of intelligence itself, as natural selection would favour systems that enhances its efficiency. A component of the hormetic response in eukaryotes is the mitochondrion, which itself relies on quantum effects such as tunnelling. This suggests that quantum effects control the stability of individual cells as well as long-lived cellular networks. Hormesis, which can be anti-inflammatory, is therefore key in maintaining the functional stability of complex systems, including the brain. In contrast, a lack of classical hormetic factors, such as physical activity, plant polyphenols, or calorie restriction, will lead to accelerated cognitive decline, which is associated with increased inflammation. However, there may be another previously unidentified factor that could also be considered hormetic, and that is thinking itself. Here we propose that the process of "thinking", and managing complex movement, induces "stress" in the neuronal system and is therefore in itself part of maintaining cognitive health and reserve throughout life. In effect, the right amount of thinking and information processing can beneficially induce adaptation, and this itself could be explainable by quantum thermodynamics.

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“…Fusion of both membranes is a two-step process that occurs in a coordinate fashion, although the precise mechanism remains unclear (Malka, Guillery et al, 2005). Mitochondrial fission requires the recruitment of dynamin-related protein 1 (Drp1) from the cytosol to the OMM where it forms multimeric rings and spiral-like structures that surround and constrict the organelle in a GTP-dependent manner (Sheridan & Martin, 2010). The mechanism that triggers this recruitment is still unknown, however, Fis1, a small mitochondrial transmembrane protein, seems to be responsible for this mobilization (Sheridan & Martin, 2010).…”

mentioning

confidence: 99%

“…Mitochondrial fission requires the recruitment of dynamin-related protein 1 (Drp1) from the cytosol to the OMM where it forms multimeric rings and spiral-like structures that surround and constrict the organelle in a GTP-dependent manner (Sheridan & Martin, 2010). The mechanism that triggers this recruitment is still unknown, however, Fis1, a small mitochondrial transmembrane protein, seems to be responsible for this mobilization (Sheridan & Martin, 2010). Mitochondria are the only organelles outside of the nucleus that contain their own genome and replicate itself in an independent manner from the nuclear genome.…”

mentioning

confidence: 99%