Intermitochondrial signaling regulates the uniform distribution of stationary mitochondria in axons

Matsumoto, Nozomu; Hori, Ikuma; Kajita, Masashi; Murase, Tomoya; Nakamura, Wataru; Tsuji, Takahiro; Miyake, Seiji; Inatani, Masaru; Konishi, Yoshiyuki

doi:10.1016/j.mcn.2022.103704

Cited by 15 publications

(15 citation statements)

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“…We calculated the Iδ index, which indicates a distribution pattern, and plotted its relationship to compartment area ratio (Figure 1c). We confirmed that the distribution of mitochondria in a single axon of RGC exhibited a uniform pattern in vivo and in vitro (control in Figure 3d, Figure 5c), as previously reported [18].…”

Section: Intra-mitochondrial Distribution In a Single Unmyelinated Rg...supporting

confidence: 91%

“…In this study, we demonstrated the way in which the mitochondrial distribution was altered within a single RGC axon in Thy1-mito-YFP mice, both in vitro and in vivo. We previously reported that the distribution of mitochondria in axons of both RGCs and primary cerebellar granule cells displayed a uniform pattern [18]. To reveal the pathophysiological role of these distributions, we introduced an ONC model to simulate a traumatic optic neuropathy or a type of glaucoma.…”

Section: Discussionmentioning

confidence: 99%

“…Mitochondria accumulate in growth cones and at branches of nerve fibers during development, as well as at the distal tips of damaged axons. On the other hand, axonal mitochondria are distributed at regular intervals in dorsal root ganglions, cerebellar granule cells, and RGCs [18,20]. Considering that mitochondria can act to buffer ATP and calcium, this regular distribution of axonal mitochondria may be involved in axonal maintenance.…”

Section: Pathophysiological Significance Of Mitochondrial Distributio...mentioning

confidence: 99%

“…The transgenic mice in which YFP with human cytochrome c oxidase subunit VIII were expressed under the regulatory element of the mouse Thy1 gene (Thy1-mito-YFP mice) were generated as previously described [18]. In total, we used 36 of these male mice at 12 to 16 weeks old.…”

Section: Animalsmentioning

confidence: 99%

“…We previously demonstrated that mitochondria are uniformly distributed in the unmyelinated parts of RGC axons in transgenic mice with visualized mitochondria. An ATP-dependent mechanism may be responsible for this distribution pattern, as we explored using primary cultured cerebellar granule cells [18]. However, the pathophysiological role of this mitochondrial distribution pattern remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Optic Nerve Injury Enhanced Mitochondrial Fission and Increased Mitochondrial Density without Altering the Uniform Mitochondrial Distribution in the Unmyelinated Axons of Retinal Ganglion Cells in a Mouse Model

Tsuji¹,

Murase²,

Konishi³

et al. 2023

Preprint

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Glaucomatous optic neuropathy, a major cause of blindness, is characterized by the loss of retinal gan-glion cells (RGCs) and degeneration of their axons. Mitochondria are deeply involved in maintaining RGCs and their axons. Therefore, lots of attempts have been made to develop diagnostic tools and therapies tar-geting mitochondria. Recently, we reported that mitochondria are uniformly distributed in unmyelinated axons of RGCs, possibly owing to the ATP gradient. Thus, using transgenic mice expressing yellow fluo-rescent protein targeting mitochondria exclusively in RGCs within the retina, we assessed the alteration of mitochondrial distributions induced by optic nerve crush (ONC) via in vitro flat-mount retinal sections and in vivo fundus images captured through the cornea with a confocal scanning ophthalmoscope. We observed that the mitochondrial distribution in unmyelinated axons of RGCs that survived the ONC remained uni-form, although their density increased. Furthermore, via in vitro analysis, we discovered that the mitochon-drial size is attenuated following ONC. These results suggest that ONC induces mitochondrial fission without disrupting the uniform mitochondrial distribution. This mechanism may help to prevent axonal degeneration and apoptosis. The in vivo visualization system of axonal mitochondria in RGCs may be ap-plicable in the diagnosis of progression of optic neuropathy.

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Section: Intra-mitochondrial Distribution In a Single Unmyelinated Rg...supporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Pathophysiological Significance Of Mitochondrial Distributio...mentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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