Importance of retrograde axonal transport in mitochondrial health and distribution

Hung, Christy

doi:10.1038/s41420-021-00502-3

Cited by 5 publications

(2 citation statements)

References 10 publications

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“…Mitochondrial dynamics in terminally differentiated cells is strictly regulated by maintaining a delicate balance between ssion, fusion and mitophagy, with e cient anterograde and retrograde transport mechanisms to factor in the complexity of axonal processes and dendritic arborizations [59].…”

Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing on a multiplex family of Indian origin identifies mutations at 17p11.2 in siblings with autism spectrum disorders: implications to understanding the pathophysiology from syndromic variants.

Srivid,

Ranganayaki,

Parambath

et al. 2023

Preprint

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Autism Spectrum Disorders (ASDs) is a complex neurodevelopmental disorder characterized by restrictive repetitive behaviour and impairment in social and communication skills. It is extremely heterogeneous with a strong genetic preponderance. It’s clinically highly convoluted, represented with multiple comorbid conditions and syndromic features. More than 100 genes have been identified till date that are associated with syndromic ASDs. Whole exome sequencing (WES) has emerged as a valuable tool in evaluating the genetic underpinnings of ASDs, be it the syndromic or the idiopathic variants. The current study leverages the utility of WES in a multiplex family of Indian origin to identify the disease etiology in the siblings (01S1 (Female) and 01S2 (Male)) exhibiting ASD syndromic features, at both clinical and molecular levels. Our systematic bioinformatic analysis identified a missense mutation (NM_030665.4:c.5320C > T; p.Arg1774Trp) in 01S1 resulting in RAI1 haploinsufficiency. Validation by sanger sequencing confirmed the novelty of the said mutation and that it was true positive and maternally transmitted in the subject. Likewise, we report a missense mutation at the same locus (17p11.2) corresponding to the FLII gene (NM_002018.4:c.2030A > C;p.Glu677Ala) in the other sibling, 01S2. Both the mutations were reported in the Smith Magenis Syndrome (SMS) critical region justifying its contribution to the presentation of the syndromic SMS features. These WES findings were consistent with the clinical findings that imply SMS features in both siblings. The current study employs WES to provide insights into the complex molecular mechanism associated with syndromic ASD highlighting the different processes that contribute to the disease heterogeneity. Moving forward, combinatorial approaches and findings from syndromic ASDs can potentially act as indicators to understand the genetic and phenotypic variations seen in the idiopathic ASD.

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Section: Discussionmentioning

confidence: 99%

Whole Exome Sequencing on a multiplex family of Indian origin identifies mutations at 17p11.2 in siblings with autism spectrum disorders: implications to understanding the pathophysiology from syndromic variants.

Srivid,

Ranganayaki,

Parambath

et al. 2023

Preprint

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“…Mitochondrial trafficking in neurons is a phenomenon in which mitochondria move bidirectionally, with anterograde transport of mitochondria from the cell body to synaptic terminals and retrograde transport of mitochondria from the synaptic terminals to the cell body [57]. Kinesin-1 mediates anterograde transport and cytoplasmic dynein motors monitor retrograde mitochondrial transport [58]. Studies show that retrograde mitochondrial transport is important for removing aged organelles, and disruption of it impacts the function of motor synapses and the homeostatic distri-bution of mitochondria throughout the neuron [59].…”

Section: Mitochondrial Traffickingmentioning

confidence: 99%

Mitochondria in Alzheimer’s Disease Pathogenesis

Reiss,

Gulkarov,

Jacob

et al. 2024

Life

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Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment.

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Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction

Ren,

Jiang,

Wang

et al. 2024

Mol Neurobiol

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Importance of retrograde axonal transport in mitochondrial health and distribution

Cited by 5 publications

References 10 publications

Whole Exome Sequencing on a multiplex family of Indian origin identifies mutations at 17p11.2 in siblings with autism spectrum disorders: implications to understanding the pathophysiology from syndromic variants.

Whole Exome Sequencing on a multiplex family of Indian origin identifies mutations at 17p11.2 in siblings with autism spectrum disorders: implications to understanding the pathophysiology from syndromic variants.

Mitochondria in Alzheimer’s Disease Pathogenesis

Loss of CHCHD2 Stability Coordinates with C1QBP/CHCHD2/CHCHD10 Complex Impairment to Mediate PD-Linked Mitochondrial Dysfunction

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