Mitochondrial biogenesis is required for axonal growth

Vaarmann, Annika; Mandel, Merle; Zeb, Akbar; Warȩski, Przemyslaw; Liiv, Joanna; Kuum, Malle; Antsov, Eva; Liiv, Mailis; Cagalinec, Michal; Choubey, Vinay; Kaasik, Allen

doi:10.1242/jcs.193037

Cited by 8 publications

(10 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, we tested whether the above‐described changes are sufficient to affect neuronal ATP levels and survival. We first estimated neuronal ATP/ADP ratio using the genetically encoded fluorescent ratiometric probe Perceval HR, which we have shown to be sufficiently sensitive to track intracellular ATP/ADP ratio in our model (Vaarmann et al , ). Glutamate treatment induced a clear and significant decrease in ATP levels that was reversed by the Miro1 EF and augmented by the Miro1 WT (Fig I).…”

Section: Resultsmentioning

confidence: 99%

“…Neuronal somas expressing the ATP/ADP ratio sensor Perceval HR were excited using a 405‐nm diode laser and a 488‐nm line of an Argon laser, and emission was collected using a 494–553‐nm window (Vaarmann et al , ). Data are expressed as the ratio of fluorescence emission from neuronal soma evoked by 488 nm excitation/405 nm excitation (F488 nm/F405 nm).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Miro proteins prime mitochondria for Parkin translocation and mitophagy

et al. 2018

Self Cite

View full text Add to dashboard Cite

The Parkinson's disease‐associated protein kinase PINK1 and ubiquitin ligase Parkin coordinate the ubiquitination of mitochondrial proteins, which marks mitochondria for degradation. Miro1, an atypical GTPase involved in mitochondrial trafficking, is one of the substrates tagged by Parkin after mitochondrial damage. Here, we demonstrate that a small pool of Parkin interacts with Miro1 before mitochondrial damage occurs. This interaction does not require PINK1, does not involve ubiquitination of Miro1 and also does not disturb Miro1 function. However, following mitochondrial damage and PINK1 accumulation, this initial pool of Parkin becomes activated, leading to the ubiquitination and degradation of Miro1. Knockdown of Miro proteins reduces Parkin translocation to mitochondria and suppresses mitophagic removal of mitochondria. Moreover, we demonstrate that Miro1 EF‐hand domains control Miro1's ubiquitination and Parkin recruitment to damaged mitochondria, and they protect neurons from glutamate‐induced mitophagy. Together, our results suggest that Miro1 functions as a calcium‐sensitive docking site for Parkin on mitochondria.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Miro proteins prime mitochondria for Parkin translocation and mitophagy

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…In neurons, proper calcium homeostasis is required for gene transcriptional regulation. After excitatory neuronal stimulation, NMDAR activation leads to synaptic Ca 2+ influx, which in turn activates the kinase CAMKII and transcription factors such as cyclic AMP response element‐binding protein (CREB) or PGC‐1a (Cohen et al, ; Vaarmann et al, ). Activated transcription factors then recruit epigenetic machinery to modulate their target gene expression, among them synaptic plasticity genes.…”

Section: Proposed Mechanisms Leading To Epigenetic Alterations In Thementioning

confidence: 99%

Epigenetic mechanisms related to cognitive decline during aging

Harman

Martín

2019

J of Neuroscience Research

View full text Add to dashboard Cite

Cognitive decline is a hallmark of the aging nervous system, characterized by increasing memory loss and a deterioration of mental capacity, which in turn creates a favorable context for the development of neurodegenerative diseases. One of the most detrimental alterations that occur at the molecular level in the brain during aging is the modification of the epigenetic mechanisms that control gene expression. As a result of these epigenetic‐driven changes in the transcriptome most of the functions of the brain including synaptic plasticity, learning, and memory decline with aging. The epigenetic mechanisms altered during aging include DNA methylation, histone modifications, nucleosome remodeling, and microRNA‐mediated gene regulation. In this review, we examine the current evidence concerning the changes of epigenetic modifications together with the molecular mechanisms underlying impaired neuronal gene transcription during aging. Herein, we discuss the alterations of DNA methylation pattern that occur in old neurons. We will also describe the most prominent age‐related histone posttranslational modifications in the brain since changes in acetylation and methylation of specific lysine residues on H3 and H4 are associated to functional decline in the old. In addition, we discuss the role that changes in the levels of certain miRNAs would play in cognitive decline with aging. Finally, we provide an overview about the mechanisms either extrinsic or intrinsic that would trigger epigenetic changes in the aging brain, and the consequences of these changes, i.e., altered transcriptional profile and reactivation of transposable elements in old brain.

show abstract

“…In the present study, elongated mitochondria were observed in neuritelike structures after neuronal differentiation of SHED. Mitochondrial localization in axons and local ATP production were required for the events of neuronal outgrowth, including growth corn motility and cytoskeletal assembly (Bernstein and Bamburg, 2003;Morris and Hollenbeck, 1993;Ruthel and Hollenbeck, 2003;Vaarmann et al, 2016). In addition, elongated mitochondria have been observed in the neurites of cortical neurons during neuronal differentiation (Cho et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Mitochondria Regulate the Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth

Kato

Pham

Yamaza

et al. 2017

Cell Struct. Funct.

View full text Add to dashboard Cite

ABSTRACT. Stem cells from human exfoliated deciduous teeth (SHED) are isolated from the dental pulp tissue of primary teeth and can differentiate into neuronal cells. Although SHED are a desirable type of stem cells for transplantation therapy and for the study of neurological diseases, a large part of the neuronal differentiation machinery of SHED remains unclear. Recent studies have suggested that mitochondrial activity is involved in the differentiation of stem cells. In the present work, we investigated the neuronal differentiation machinery of SHED by focusing on mitochondrial activity. During neuronal differentiation of SHED, we observed increased mitochondrial membrane potential, increased mitochondrial DNA, and elongated mitochondria. Furthermore, to examine the demand for mitochondrial activity in neuronal differentiation, we then differentiated SHED into neuronal cells in the presence of rotenone, an inhibitor of mitochondrial respiratory chain complex I, and carbonyl cyanide m-chlorophenyl hydrazone (CCCP), a mitochondrial uncoupler, and found that neuronal differentiation was inhibited by treatment with rotenone and CCCP. These results indicated that increased mitochondrial activity was crucial for the neuronal differentiation of SHED.

show abstract

Mitochondrial biogenesis is required for axonal growth

Cited by 8 publications

References 15 publications

Miro proteins prime mitochondria for Parkin translocation and mitophagy

Miro proteins prime mitochondria for Parkin translocation and mitophagy

Epigenetic mechanisms related to cognitive decline during aging

Mitochondria Regulate the Differentiation of Stem Cells from Human Exfoliated Deciduous Teeth

Contact Info

Product

Resources

About