Dataset Information

Mitochondrial Protrusions in Neuronal Cells.

ABSTRACT: Mitochondrial function relies on multiple quality control mechanisms, including the release of mitochondrial vesicles. To investigate the ultrastructure and prevalence of mitochondrial membranous protrusions (and, by extension, vesicles) in neurons, we surveyed mitochondria in rat and planarian brains using transmission electron microscopy (EM). We observed that mitochondrial protrusions mostly extend from the outer membrane. Leveraging available 3D EM datasets of the brain, we further analyzed mitochondrial protrusions in neurons of mouse and Drosophila brains, identifying high-resolution spatial views of these protrusions. To assess whether the abundance of mitochondrial protrusions and mitochondria-derived vesicles respond to cellular stress, we examined neurons expressing fluorescently tagged mitochondrial markers using confocal microscopy with Airyscan and found increased numbers of mitochondrial protrusions and vesicles with mild stress. Future studies using improved spatial resolution with added temporal information may further define the functional implications of mitochondrial protrusions and vesicles in neurons.

SUBMITTER: Yao PJ

PROVIDER: S-EPMC7501463 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Mitochondrial Protrusions in Neuronal Cells.

Yao Pamela J PJ Eren Erden E Petralia Ronald S RS Gu Jeffrey W JW Wang Ya-Xian YX Kapogiannis Dimitrios D

iScience 20200829 9

Mitochondrial function relies on multiple quality control mechanisms, including the release of mitochondrial vesicles. To investigate the ultrastructure and prevalence of mitochondrial membranous protrusions (and, by extension, vesicles) in neurons, we surveyed mitochondria in rat and planarian brains using transmission electron microscopy (EM). We observed that mitochondrial protrusions mostly extend from the outer membrane. Leveraging available 3D EM datasets of the brain, we further analyzed ...[more]

PMID: 32942173

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Project description:Maintaining mitochondrial function is essential for neuronal survival and offers protection against neurodegeneration. Ubiquitin-mediated, proteasome-dependent protein degradation in the form of outer mitochondrial membrane associated degradation (OMMAD) was shown to play roles in maintenance of mitochondria on the level of proteostasis, but also mitophagy and cell death. Recently, the AAA-ATPase p97/VCP/Cdc48 was recognized as part of OMMAD acting as retrotranslocase of ubiquitinated mitochondrial proteins for proteasomal degradation. Thus, p97 likely plays a major role in mitochondrial maintenance. Support for this notion comes from mitochondrial dysfunction associated with amyotrophic lateral sclerosis and hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia (IBMPFD) caused by p97 mutation. Using SH-SY5Y cells stably expressing p97 or dominant-negative p97(QQ) treated with mitochondrial toxins rotenone, 6-OHDA, or Aβ-peptide as model for neuronal cells suffering from mitochondrial dysfunction, we found mitochondrial fragmentation under normal and stress conditions was significantly increased upon inactivation of p97. Furthermore, inactivation of p97 resulted in loss of mitochondrial membrane potential and increased production of reactive oxygen species (ROS). Under additional stress conditions, loss of mitochondrial membrane potential and increased ROS production was even more pronounced. Loss of mitochondrial fidelity upon inactivation of p97 was likely due to disturbed maintenance of mitochondrial proteostasis as the employed treatments neither induced mitophagy nor cell death. This was supported by the accumulation of oxidatively-damaged proteins on mitochondria in response to p97 inactivation. Dysfunction of p97 under normal and stress conditions in neuron-like cells severely impacts mitochondrial function, thus supporting for the first time a role for p97 as a major component of mitochondrial proteostasis.

Dataset Information

Mitochondrial Protrusions in Neuronal Cells.

Publications

Mitochondrial Protrusions in Neuronal Cells.

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