Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture

Misgeld, Thomas; Schwarz, Thomas L.

doi:10.1016/j.neuron.2017.09.055

Cited by 405 publications

(453 citation statements)

References 143 publications

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“…Disturbances of mitochondrial fusion or fission have been shown to correlate with mitochondrial trafficking defects (Sheng, ; Misgeld & Schwarz, ). Therefore, we examined the morphology of the mitochondrial network in spinal cord and brain of NYKO mice.…”

Section: Resultsmentioning

confidence: 99%

Loss of the mitochondrial i ‐ AAA protease YME 1L leads to ocular dysfunction and spinal axonopathy

et al. 2018

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Disturbances in the morphology and function of mitochondria cause neurological diseases, which can affect the central and peripheral nervous system. The i‐AAA protease YME1L ensures mitochondrial proteostasis and regulates mitochondrial dynamics by processing of the dynamin‐like GTPase OPA1. Mutations in YME1L cause a multi‐systemic mitochondriopathy associated with neurological dysfunction and mitochondrial fragmentation but pathogenic mechanisms remained enigmatic. Here, we report on striking cell‐type‐specific defects in mice lacking YME1L in the nervous system. YME1L‐deficient mice manifest ocular dysfunction with microphthalmia and cataracts and develop deficiencies in locomotor activity due to specific degeneration of spinal cord axons, which relay proprioceptive signals from the hind limbs to the cerebellum. Mitochondrial fragmentation occurs throughout the nervous system and does not correlate with the degenerative phenotype. Deletion of Oma1 restores tubular mitochondria but deteriorates axonal degeneration in the absence of YME1L, demonstrating that impaired mitochondrial proteostasis rather than mitochondrial fragmentation causes the observed neurological defects.

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Section: Resultsmentioning

confidence: 99%

Loss of the mitochondrial i ‐ AAA protease YME 1L leads to ocular dysfunction and spinal axonopathy

et al. 2018

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“…Mitochondrial motility is especially important during neuronal outgrowth, but this motility is dramatically reduced in mature neurons, with <10% of mitochondria motile along the axons of mature mammalian neurons both in vitro and in vivo [13,14]. …”

Section: Dynamic Interactions Of Mitochondria With Microtubulesmentioning

confidence: 99%

Mitochondrial-cytoskeletal interactions: dynamic associations that facilitate network function and remodeling

Moore

Holzbaur

2018

Current Opinion in Physiology

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Mitochondria are dynamic organelles that can form complex networks in the cell. These networks can be rapidly remodeled in response to environmental changes or to support cellular needs. Mitochondrial dynamics are dependent on interactions with the cellular cytoskeleton – both microtubules and actin filaments. Mitochondrial-cytoskeletal interactions have a well-established role in mitochondrial motility. Recent progress indicates that these interactions also regulate the balance of mitochondrial fission/fusion, as well as mitochondria turnover and mitochondrial inheritance during cell division. We review these advances, and how this work has deepened our understanding of mitochondrial dynamics in the cell.

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“…32,33 Because mitochondrial biogenesis is balanced by removal of damaged mitochondria, 34 Crls1 deficiency driven by Camk2α-Cre transgene (hereafter referred to as CCre) could change the CL content in mitochondria of the neurons in a slower pace. In this study, we used Camk2α-Cre transgenic mice in which Cre recombinase was expressed in subsets of postmitotic neurons throughout the forebrain.…”

Section: Generation Of Postmitotic Neuronspecific Crls1 Knockout Micementioning

confidence: 99%

Cardiolipin is essential for early embryonic viability and mitochondrial integrity of neurons in mammals

et al. 2019

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Cardiolipin (CL) is a hallmark phospholipid of mitochondria and plays a significant role in maintaining the mitochondrial structure and functions. Despite the physiological importance of CL, mutant organisms, yeast, Arabidopsis, C elegans, and Drosophila, which lack CL synthase (Crls1) gene and consequently are deprived of CL, are viable. Here we report conditional Crls1-deficient mice using targeted insertion of loxP sequences flanking the functional domain of CRLS1 enzyme.Homozygous null mutant mice exhibited early embryonic lethality at the peri-implantation stage. We generated neuron-specific Crls1 knockout (cKO) mice by crossing with Camk2α-Cre mice. Neuronal loss and gliosis were gradually manifested in the forebrains, where CL levels were significantly decreased. In the surviving neurons, malformed mitochondria with bubble-like or onion-like inner membrane structures were observed. We showed decreased supercomplex assembly and reduced enzymatic activities of electron transport chain complexes in the forebrain of cKO mice, resulting in affected mitochondrial calcium dynamics, a slower rate of Ca 2+ uptake and a smaller calcium retention capacity. These observations clearly demonstrate indispensable roles of CL as well as of Crls1 gene in mammals.

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Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture

Cited by 405 publications

References 143 publications

Loss of the mitochondrial i ‐ AAA protease YME 1L leads to ocular dysfunction and spinal axonopathy

Loss of the mitochondrial i ‐ AAA protease YME 1L leads to ocular dysfunction and spinal axonopathy

Mitochondrial-cytoskeletal interactions: dynamic associations that facilitate network function and remodeling

Cardiolipin is essential for early embryonic viability and mitochondrial integrity of neurons in mammals

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