Miro—Working beyond Mitochondria and Microtubules

Tang, Bor Luen

doi:10.3390/cells7030018

Cited by 13 publications

(11 citation statements)

References 36 publications

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“…The linker protein Milton and its binding partner Miro (a small GTPase) link the C-terminus of Khc to organelles including mitochondria (Fig.3A,Biii;Harbauer, 2017;Misgeld and Schwarz, 2017;Sheng, 2017;Smith and Gallo, 2018) and potentially peroxisomes (Castro et al, 2018;Covill-Cooke et al, 2017;Okumoto et al, 2018;Tang, 2018).…”

Section: Loss Of Milton and Miro Causes Mt Curling Phenotypesmentioning

confidence: 99%

New cell biological explanations for kinesin-linked axon degeneration

Liew

Voelzmann

Pinho-Correia

et al. 2021

Preprint

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Axons are the slender, up to meter-long projections of neurons that form the biological cables wiring our bodies. Most of these delicate structures must survive for an organism's lifetime, meaning up to a century in humans. Axon maintenance requires life-sustaining motor protein-driven transport distributing materials and organelles from the distant cell body. It seems logic that impairing this transport causes systemic deprivation linking to axon degeneration. But the key steps underlying these pathological processes are little understood. To investigate mechanisms triggered by motor protein aberrations, we studied more than 40 loss- and gain-of-function conditions of motor proteins, cargo linkers or further genes involved in related processes of cellular physiology. We used one standardised Drosophila primary neuron system and focussed on the organisation of axonal microtubule bundles as an easy to assess readout reflecting axon integrity. We found that bundle disintegration into curled microtubules is caused by the losses of Dynein heavy chain and the Kif1 and Kif5 homologues Unc-104 and Kinesin heavy chain (Khc). Using point mutations of Khc and functional loss of its linker proteins, we studied which of Khc's sub-functions might link to microtubule curling. One cause was emergence of harmful reactive oxygen species through loss of Milton/Miro-mediated mitochondrial transport. In contrast, loss of the Kinesin light chain linker caused microtubule curling through an entirely different mechanism appearing to involve increased mechanical challenge to microtubule bundles through de-inhibition of Khc. The wider implications of our findings for the understanding of axon maintenance and pathology are discussed.

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Section: Loss Of Milton and Miro Causes Mt Curling Phenotypesmentioning

confidence: 99%

New cell biological explanations for kinesin-linked axon degeneration

Liew

Voelzmann

Pinho-Correia

et al. 2021

Preprint

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“…Dysferlin is involved in T-tubule formation and vesicle trafficking [30]. The small GTPase miro regulates mitochondrial trafficking along MTs by acting as a receptor for mitochondrial recruitment of the TRAK adaptors to drive movements mediated by the MT-based motor proteins-kinesin and dynein [31]. In the GA ( Figure 3A), the mRNA levels for MIRO1, kinesin (KIF5B), and dynein (DYNC1H1) were elevated (~+100% vs. Con, p < 0.05) during immobilization and were either normalized (MIRO1, DYNC1H1) or reduced (KIF5B) during remobilization.…”

Section: Mitochondria Trafficking Along Microtubules Was Induced In Bmentioning

confidence: 99%

Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization

Deval

Calonne

Coudy-Gandilhon

et al. 2020

IJMS

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Mitochondria alterations are a classical feature of muscle immobilization, and autophagy is required for the elimination of deficient mitochondria (mitophagy) and the maintenance of muscle mass. We focused on the regulation of mitochondrial quality control during immobilization and remobilization in rat gastrocnemius (GA) and tibialis anterior (TA) muscles, which have very different atrophy and recovery kinetics. We studied mitochondrial biogenesis, dynamic, movement along microtubules, and addressing to autophagy. Our data indicated that mitochondria quality control adapted differently to immobilization and remobilization in GA and TA muscles. Data showed i) a disruption of mitochondria dynamic that occurred earlier in the immobilized TA, ii) an overriding role of mitophagy that involved Parkin-dependent and/or independent processes during immobilization in the GA and during remobilization in the TA, and iii) increased mitochondria biogenesis during remobilization in both muscles. This strongly emphasized the need to consider several muscle groups to study the mechanisms involved in muscle atrophy and their ability to recover, in order to provide broad and/or specific clues for the development of strategies to maintain muscle mass and improve the health and quality of life of patients.

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“…Mitochondrial Rho-GTPase, or Miro, is an outer membrane receptor, Ca 2+ sensor, and another pertinent regulator of mitochondrial motility due to its ability to anchor kinesin and dynein to the mitochondrial outer membrane [43]. Miro's anchoring role has been extensively studied in anterograde movement in the motor/ adaptor complex formed between KHC and Miro, connected by the protein adaptor milton [44,45].…”

Section: Mitochondrial Traffickingmentioning

confidence: 99%

Lifestyle Factors, Mitochondrial Dynamics, and Neuroprotection

Broman¹,

Davis²,

May³

et al. 2020

Neuroprotection - New Approaches and Prospects

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The brain requires vast amounts of energy to carry out neurotransmission; indeed, it is responsible for approximately one-fifth of the body’s energy consumption. Therefore, in order to understand functions of brain cells under both normal and pathological conditions, it is critical to elucidate dynamics of intracellular energy. The mitochondrion is the key intercellular organelle that controls neuronal energy and survival. Numerous studies have reported a correlation between altered mitochondrial function and brain-associated diseases; thus mitochondria may serve as a promising target for treating these conditions. In this chapter, we will discuss the mechanisms of mitochondrial production, movement, and degradation in order to understand accessibility of energy during physiological and pathological conditions of the brain. While research targeting molecular dynamics is promising, translation into clinical relevance based on bench research is challenging. For these reasons, we will also summarize lifestyle factors, including interventions and chronic comorbidities that disrupt mitochondrial dynamics. By determining lifestyle factors that are readily accessible, we can propose a new viewpoint for a synergistic and translational approach for neuroprotection.

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Miro—Working beyond Mitochondria and Microtubules

Cited by 13 publications

References 36 publications

New cell biological explanations for kinesin-linked axon degeneration

New cell biological explanations for kinesin-linked axon degeneration

Mitophagy and Mitochondria Biogenesis Are Differentially Induced in Rat Skeletal Muscles during Immobilization and/or Remobilization

Lifestyle Factors, Mitochondrial Dynamics, and Neuroprotection

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