Miro proteins connect mitochondrial function and intercellular transport

Nahácka, Zuzana; Zobalova, Renata; Dubisova, Maria; Rohlena, Jakub; Neužil, Jiřı́

doi:10.1080/10409238.2021.1925216

Cited by 15 publications

(14 citation statements)

References 220 publications

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“…It was already described that in PD aSyn has a specific functional role in mitochondrial homeostasis and distribution [67,68]. These highly dynamic organelles provide energy and regulate a variety of cellular processes in healthy conditions [69]. Therefore, we hypothesized that aSyn plays an important role in mitochondrial distribution and affects intracellular transport processes in melanocytes mediated by mitochondrial energy supply.…”

Section: Alpha-synuclein and Mitochondriamentioning

confidence: 93%

Alpha-Synuclein and Its Role in Melanocytes

Rachinger

Mittag

Böhme-Schäfer

et al. 2022

Cells

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Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson’s disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.

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Section: Alpha-synuclein and Mitochondriamentioning

confidence: 93%

Alpha-Synuclein and Its Role in Melanocytes

Rachinger

Mittag

Böhme-Schäfer

et al. 2022

Cells

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“…Les protéines Miro1 et Miro2 sont des Rho GTPases (ou petites GTPases) mitochondriales codées, chez l'homme, par les gènes RHOT1 et RHOT2. Elles sont ancrées dans la membrane externe de la mitochondrie par leur extrémité C-terminale [5,6]. Complexées aux protéines TRAK1/2 (trafficking kinesin 1/2) (Milton chez la drosophile), Miro 1 et 2 jouent un rôle d'adaptateurs entre la membrane des mitochondries et les microtubules de la cellule (Figure 1).…”

Section: Transport Des Mitochondries : Le Paradigme Des Neuronesunclassified

Le transport mitochondrial

2022

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La reprogrammation métabolique est l’un des marqueurs de la carcinogenèse. Au cœur de cette reprogrammation se trouvent les mitochondries qui produisent l’énergie sous forme de molécules d’ATP. La régulation spatio-temporelle de la production d’ATP, indispensable pour fournir l’énergie au bon endroit et au bon moment, est assurée par le transport intracellulaire des mitochondries. Les complexes Miro/TRAK présents à la surface des mitochondries se lient aux protéines motrices de la cellule (dynéine, kinésine, myosine) pour transporter les mitochondries le long du cytosquelette. Ces acteurs du transport mitochondrial sont souvent dérégulés dans le cancer. Nous présentons dans cette revue les mécanismes par lesquels le transport mitochondrial contribue à la migration, à la division cellulaire et à la réponse au stress des cellules cancéreuses. Décrypter ces mécanismes pourrait ouvrir la voie à de nouvelles approches thérapeutiques en oncologie.

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“…The rescue capacity of MSCs mediated via TNTs correlates with the Miro-1 expression, as shown for the transfer capacity of mitochondria from MSCs to stressed alveolar epithelial cells via TNTs [ 9 ]. Miro-1 and -2 belong to a class of novel Rho-GTPase, amino acid sequence revealed GTPases domain homolog to the classical Rho-GTPases in the N-terminal part of the protein [ 16 ]. Interestingly, Miro proteins lack the membrane-binding motif CAAX in their C-terminal domains, unlike small GTPases but contain a second GTP-binding domain without homology to typical Rho-GTPases [ 15 ].…”

Section: Rho Gtpase Related Signals Counteract Apoptosis Via Tunnelling Nanotubesmentioning

confidence: 99%

“…It has become evident that classical Rho GTPases (Rac1, Cdc42, and RhoA) control the complex regulatory balance in cell cycle progression and apoptotic signalling pathways [ 13 , 14 ]. The capacity of MSCs to donate healthy mitochondria to targeted acceptor cells via TNTs correlates with the activity and expression of the atypical mitochondrial Rho GTPases [ 15 ], Miro-1 [ 9 ] and Miro-2 [ 16 ]. In this review, we summarize the role of TNTs in counteracting oxidative stress, mitochondrial heteroplasmy and apoptosis-related diverse cellular stresses, and the possible association of Rho GTPase-linked apoptotic signalling pathways in cytoskeleton remodelling and plasma membrane surface dynamics in the biogenesis of TNTs.…”

Section: Introductionmentioning

confidence: 99%

Oxidative stress and Rho GTPases in the biogenesis of tunnelling nanotubes: implications in disease and therapy

Raghavan

Rao

Neužil

et al. 2021

Cell. Mol. Life Sci.

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Tunnelling nanotubes (TNTs) are an emerging route of long-range intercellular communication that mediate cell-to-cell exchange of cargo and organelles and contribute to maintaining cellular homeostasis by balancing diverse cellular stresses. Besides their role in intercellular communication, TNTs are implicated in several ways in health and disease. Transfer of pathogenic molecules or structures via TNTs can promote the progression of neurodegenerative diseases, cancer malignancy, and the spread of viral infection. Additionally, TNTs contribute to acquiring resistance to cancer therapy, probably via their ability to rescue cells by ameliorating various pathological stresses, such as oxidative stress, reactive oxygen species (ROS), mitochondrial dysfunction, and apoptotic stress. Moreover, mesenchymal stem cells play a crucial role in the rejuvenation of targeted cells with mitochondrial heteroplasmy and oxidative stress by transferring healthy mitochondria through TNTs. Recent research has focussed on uncovering the key regulatory molecules involved in the biogenesis of TNTs. However further work will be required to provide detailed understanding of TNT regulation. In this review, we discuss possible associations with Rho GTPases linked to oxidative stress and apoptotic signals in biogenesis pathways of TNTs and summarize how intercellular trafficking of cargo and organelles, including mitochondria, via TNTs plays a crucial role in disease progression and also in rejuvenation/therapy.

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Miro proteins connect mitochondrial function and intercellular transport

Cited by 15 publications

References 220 publications

Alpha-Synuclein and Its Role in Melanocytes

Alpha-Synuclein and Its Role in Melanocytes

Le transport mitochondrial

Oxidative stress and Rho GTPases in the biogenesis of tunnelling nanotubes: implications in disease and therapy

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