Mitochondrial dynamics–fusion, fission, movement, and mitophagy–in neurodegenerative diseases

By Hsiuchen Chen, D. C. Chan. Human Molecular Genetics, 2009

1,468 citations recorded by the source corpus.

Neurons are metabolically active cells with high energy demands at locations distant from the cell body. As a result, these cells are particularly dependent on mitochondrial function, as reflected by the observation that diseases of mitochondrial dysfunction often have a neurodegenerative component. Recent discoveries have highlighted that neurons are reliant particularly on the dynamic properties of mitochondria. Mitochondria are dynamic organelles by several criteria. They engage in repeated cycles of fusion and fission, which serve to intermix the lipids and contents of a population of mitochondria. In addition, mitochondria are actively recruited to subcellular sites, such as the axonal and dendritic processes of neurons. Finally, the quality of a mitochondrial population is maintained through mitophagy, a form of autophagy in which defective mitochondria are selectively degraded. We review the general features of mitochondrial dynamics, incorporating recent findings on mitochondrial fusion, fission, transport and mitophagy. Defects in these key features are associated with neurodegenerative disease. Charcot-Marie-Tooth type 2A, a peripheral neuropathy, and dominant optic atrophy, an inherited optic neuropathy, result from a primary deficiency of mitochondrial fusion. Moreover, several major neurodegenerative diseases—including Parkinson's, Alzheimer's and Huntington's disease—involve disruption of mitochondrial dynamics. Remarkably, in several disease models, the manipulation of mitochondrial fusion or fission can partially rescue disease phenotypes. We review how mitochondrial dynamics is altered in these neurodegenerative diseases and discuss the reciprocal interactions between mitochondrial fusion, fission, transport and mitophagy.

Subfields: Cellular and Molecular Neuroscience, Clinical Biochemistry, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/bcabe5850fc62924cd4ff39b8a23574bb566f525

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cellular and Molecular Neuroscience

1. P. Reddy
2. Xia Zhang
3. Wei-Wei Chen
4. Wenjuan Huang

In Clinical Biochemistry

1. Xia Zhang
2. Wei-Wei Chen
3. Wen Chen
4. Yongsheng Li
5. Wenjuan Huang
6. Huakan Zhao

In Molecular Biology

1. M. Calkins
2. M. Mańczak
3. P. Reddy
4. Xia Zhang
5. Wei-Wei Chen
6. Wen Chen
7. Yongsheng Li
8. Wenjuan Huang

Citations in the corpus

• Role of neuroinflammation in neurodegenerative diseases (Review) (2016, positive): “…neurotoxic mediators are, in general, associated with several neurodegenerative diseases including AD, MS, PD and ALS, which are commonly linked to intracellular mechanisms such as the degradation of protein, the dysfunction of mitochondria, the defects of axonal transport and apoptosis (20-22).”
• Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage. (2011, background): “However, most of Drp1 is localized in the cytoplasm, but a small part is localized in the outer membrane, where it punctuates and promotes mitochondrial fragmentation (34).”
• Mitochondrial dynamics in health and disease: mechanisms and potential targets (2023, background): “Emerging evidence strongly indicates that gene mutations in fl uencing mitochondrial dynamics are crucial to the development of PD. 175 Parkin, a protein encoded by the PARK2 gene, is implicated in PD. 176 A cytosolic ubiquitin E3 ligase protein, Parkin plays an important role in the process of ubiqu”
• Mitochondria, oxidative stress and neurodegeneration. (2012, background): “Phosphatase and tensin homologue (PTEN)-induced kinase 1 (PINK1) is a mitochondrial kinase that seems to have protective effects against cell death by suppressing release of cytochrome c bymitochondria [63].”
• The axonal transport of mitochondria (2005, background): “based machinery that drives it can cause or contribute to a number of human neurodegenerative conditions, including spastic paraplegia, Charcot–Marie–Tooth, amyotrophic lateral sclerosis and Alzheimer’s, Huntington’s and Parkinson’s disease (Blackstone et al., 2011; Chen and Chan, 2009; Chevalier-La”