Shared structural features of Miro binding control mitochondrial homeostasis.

Miro proteins are universally conserved mitochondrial calcium-binding GTPases that regulate a multitude of mitochondrial processes, including transport, clearance, and lipid trafficking. The exact role of Miro in these functions is unclear but involves binding to a variety of client proteins. How this binding is operated at the molecular level and whether and how it is important for mitochondrial health, however, remains unknown. Here, we show that known Miro interactors-namely, CENPF, Trak, and MYO19-all use a similar short motif to bind the same structural element: a highly conserved hydrophobic pocket in the first calcium-binding domain of Miro. Using these Miro-binding motifs, we identified direct interactors de novo, including MTFR1/2/1L, the lipid transporters Mdm34 and VPS13D, and the ubiquitin E3-ligase Parkin. Given the shared binding mechanism of these functionally diverse clients and its conservation across eukaryotes, we propose that Miro is a universal mitochondrial adaptor coordinating mitochondrial health.

Mitochondrial regulation of local supply of energy in neurons.

Brain computation is metabolically expensive and requires the supply of significant amounts of energy. Mitochondria are highly specialized organelles whose main function is to generate cellular energy. Due to their complex morphologies, neurons are especially dependent on a set of tools necessary to regulate mitochondrial function locally in order to match energy provision with local demands. By regulating mitochondrial transport, neurons control the local availability of mitochondrial mass in response to changes in synaptic activity. Neurons also modulate mitochondrial dynamics locally to adjust metabolic efficiency with energetic demand. Additionally, neurons remove inefficient mitochondria through mitophagy. Neurons coordinate these processes through signalling pathways that couple energetic expenditure with energy availability. When these mechanisms fail, neurons can no longer support brain function giving rise to neuropathological states like metabolic syndromes or neurodegeneration.

Mitochondrial Ca2+ uniporter haploinsufficiency enhances long-term potentiation at hippocampal mossy fibre synapses.

Long-term changes in synaptic strength form the basis of learning and memory. These changes rely upon energy-demanding mechanisms, which are regulated by local Ca2+ signalling. Mitochondria are optimised for providing energy and buffering Ca2+. However, our understanding of the role of mitochondria in regulating synaptic plasticity is incomplete. Here, we have used optical and electrophysiological techniques in cultured hippocampal neurons and ex vivo hippocampal slices from mice with haploinsufficiency of the mitochondrial Ca2+ uniporter (MCU+/-) to address whether reducing mitochondrial Ca2+ uptake alters synaptic transmission and plasticity. We found that cultured MCU+/- hippocampal neurons have impaired Ca2+ clearance, and consequently enhanced synaptic vesicle fusion at presynapses occupied by mitochondria. Furthermore, long-term potentiation (LTP) at mossy fibre (MF) synapses, a process which is dependent on presynaptic Ca2+ accumulation, is enhanced in MCU+/- slices. Our results reveal a previously unrecognised role for mitochondria in regulating presynaptic plasticity of a major excitatory pathway involved in learning and memory.

Urban landscape and infection risk in free-roaming cats.

Despite public concern on the role of free-roaming cats as reservoirs of zoonotic agents, little is known about the influence of urban and peri-urban landscapes on the exposure risk. We evaluated the seroprevalence of three zoonotic agents (Chlamydia felis, Coxiella burnetii and Toxoplasma gondii) in domestic cats (Felis catus). Two hundred and ninety-one free-roaming cats were trapped in Murcia municipality (Southeast Spain), and their sera were tested for specific antibodies against T. gondii using a modified agglutination test (MAT), and for C. felis, C. burnetii and feline immunodeficiency virus (FIV) antibodies with ELISA technique. Pathogen seroprevalence at 95% CI was calculated for each sex and age category (up to and over 12 months) and compared with a chi-squared test. The role of human population density and urban landscape characteristics on the risk of pathogen exposure in the cat population was explored using generalized linear models. Seropositivity against a single pathogen was found in 60% of the cats, while 19% was seropositive for two or three pathogens. Seroprevalence of C. felis was 8% (CI95% : 5-11), 37% (CI95% : 31-42) for C. burnetii and 42% (CI95% : 36-47) for T. gondii. In addition to these three pathogens, FIV seropositivity was low (1%, CI95% : -0.1 to 2) and adult cats were more likely to be seropositive to C. burnetii than young individuals (OR: 2.3, CI95% : 1.2-4.2). No sex or age class differences in seroprevalence were observed for the rest of the pathogens. Seropositivity was correlated with water surface areas for C. felis, and not with crop areas. Coxiella burnetii seropositivity was correlated with the percentage of urban areas (continuous with only buildings and discontinuous, that include buildings, parks, and pedestrian and urban green areas), human population size and peri-urban areas with shrubs, and not correlated with other agricultural landscapes (orchards and crop areas). However, the seroprevalence of T. gondii was only associated with agricultural landscapes such as orchards. The detection of hotspot areas of high pathogen exposure risk is the basis for municipal services to implement surveillance and risk factor control campaigns in specific-risk areas, including (a) efficient health management of urban cat colonies by geographical location, population census and health status monitoring of the components of each cat colony, (b) improvement of hygiene and sanitary conditions at the feeding points of the cat colony and (c) free-roaming cat trapping for health monitoring and, in the long term, to know the evolution of the health status of their populations.

Loss of neuronal Miro1 disrupts mitophagy and induces hyperactivation of the integrated stress response.

Clearance of mitochondria following damage is critical for neuronal homeostasis. Here, we investigate the role of Miro proteins in mitochondrial turnover by the PINK1/Parkin mitochondrial quality control system in vitro and in vivo. We find that upon mitochondrial damage, Miro is promiscuously ubiquitinated on multiple lysine residues. Genetic deletion of Miro or block of Miro1 ubiquitination and subsequent degradation lead to delayed translocation of the E3 ubiquitin ligase Parkin onto damaged mitochondria and reduced mitochondrial clearance in both fibroblasts and cultured neurons. Disrupted mitophagy in vivo, upon post-natal knockout of Miro1 in hippocampus and cortex, leads to a dramatic increase in mitofusin levels, the appearance of enlarged and hyperfused mitochondria and hyperactivation of the integrated stress response (ISR). Altogether, our results provide new insights into the central role of Miro1 in the regulation of mitochondrial homeostasis and further implicate Miro1 dysfunction in the pathogenesis of human neurodegenerative disease.

Miro1-dependent mitochondrial dynamics in parvalbumin interneurons.

The spatiotemporal distribution of mitochondria is crucial for precise ATP provision and calcium buffering required to support neuronal signaling. Fast-spiking GABAergic interneurons expressing parvalbumin (PV+) have a high mitochondrial content reflecting their large energy utilization. The importance for correct trafficking and precise mitochondrial positioning remains poorly elucidated in inhibitory neurons. Miro1 is a Ca²+-sensing adaptor protein that links mitochondria to the trafficking apparatus, for their microtubule-dependent transport along axons and dendrites, in order to meet the metabolic and Ca2+-buffering requirements of the cell. Here, we explore the role of Miro1 in PV+ interneurons and how changes in mitochondrial trafficking could alter network activity in the mouse brain. By employing live and fixed imaging, we found that the impairments in Miro1-directed trafficking in PV+ interneurons altered their mitochondrial distribution and axonal arborization, while PV+ interneuron-mediated inhibition remained intact. These changes were accompanied by an increase in the ex vivo hippocampal γ-oscillation (30-80 Hz) frequency and promoted anxiolysis. Our findings show that precise regulation of mitochondrial dynamics in PV+ interneurons is crucial for proper neuronal signaling and network synchronization.

Otodectes cynotis in urban and peri-urban semi-arid areas: a widespread parasite in the cat population.

The ear mite Otodectes cynotis is a parasite of cats and dogs of considerable veterinary importance, being the most common etiological agent of otitis externa in pets. This study investigates the presence of this parasite in 296 cats from Murcia municipality (SE Spain), and describes possible factors associated with the infestation. Cats were grouped by sex, age, lifestyle, season and provenience. Scraping samples were examined by a microscope to identify the mite. Chi square test was computed and odds ratio was used to measure the association of risk factors with parasite prevalence. Additionally, the spatial distribution of prevalences was investigated and represented through GIS software. Around 30% of the cats (CI95 25-35%) were found positives to O. cynotis. The mite infestation was significantly higher in adult cats, during the winter and in individuals from peri-urban areas. The ectoparasite was found to be widely distributed in the cat population of the study area, with an increased risk of infestation in specific peri-urban areas. The results highlight that O. cynotis is a common parasite in areas with Mediterranean semi-arid climate. Given the importance of otodectic mange, and considering that O. cynotis is not a parasite specific to cats, but may also affect dogs and wild carnivores, the information provided by this study is of great value to both pet owners and veterinarian practitioners, and it might help to implement appropriate preventive and control strategies, mainly in free-roaming cats.

Peroxisomal fission is modulated by the mitochondrial Rho-GTPases, Miro1 and Miro2.

Peroxisomes are essential for a number of cellular functions, including reactive oxygen species metabolism, fatty acid ß-oxidation and lipid synthesis. To ensure optimal functionality, peroxisomal size, shape and number must be dynamically maintained; however, many aspects of how this is regulated remain poorly characterised. Here, we show that the localisation of Miro1 and Miro2-outer mitochondrial membrane proteins essential for mitochondrial trafficking-to peroxisomes is not required for basal peroxisomal distribution and long-range trafficking, but rather for the maintenance of peroxisomal size and morphology through peroxisomal fission. Mechanistically, this is achieved by Miro negatively regulating Drp1-dependent fission, a function that is shared with the mitochondria. We further find that the peroxisomal localisation of Miro is regulated by its first GTPase domain and is mediated by an interaction through its transmembrane domain with the peroxisomal-membrane protein chaperone, Pex19. Our work highlights a shared regulatory role of Miro in maintaining the morphology of both peroxisomes and mitochondria, supporting a crosstalk between peroxisomal and mitochondrial biology.

Axonal autophagosome maturation defect through failure of ATG9A sorting underpins pathology in AP-4 deficiency syndrome.

Adaptor protein (AP) complexes mediate key sorting decisions in the cell through selective incorporation of transmembrane proteins into vesicles. Little is known of the roles of AP-4, despite its loss of function leading to a severe early onset neurological disorder, AP-4 deficiency syndrome. Here we demonstrate an AP-4 epsilon subunit knockout mouse model that recapitulates characteristic neuroanatomical phenotypes of AP-4 deficiency patients. We show that ATG9A, critical for autophagosome biogenesis, is an AP-4 cargo, which is retained within the trans-Golgi network (TGN) in vivo and in culture when AP-4 function is lost. TGN retention results in depletion of axonal ATG9A, leading to defective autophagosome generation and aberrant expansions of the distal axon. The reduction in the capacity to generate axonal autophagosomes leads to defective axonal extension and de novo generation of distal axonal swellings containing accumulated ER, underlying the impaired axonal integrity in AP-4 deficiency syndrome.Abbreviations: AP: adaptor protein; AP4B1: adaptor-related protein complex AP-4, beta 1; AP4E1: adaptor-related protein complex AP-4, epsilon 1; ATG: autophagy-related; EBSS: Earle's balanced salt solution; ER: endoplasmic reticulum; GFAP: glial fibrillary acidic protein; GOLGA1/Golgin-97/GOLG97: golgi autoantigen, golgin subfamily a, 1; GOLGA2/GM130: golgi autoantigen, golgin subfamily a, 2; HSP: hereditary spastic paraplegia; LC3/MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAP2: microtubule-associated protein 2; MAPK8IP1/JIP1: mitogen-acitvated protein kinase 8 interacting protein 1; NEFH/NF200: neurofilament, heavy polypeptide; RBFOX3/NeuN (RNA binding protein, fox-1 homolog [C. elegans] 3); SQSTM1/p62: sequestosome 1; TGN: trans-Golgi network; WIPI2: WD repeat domain, phosphoinositide interacting protein 2.

Miro clusters regulate ER-mitochondria contact sites and link cristae organization to the mitochondrial transport machinery.

Mitochondrial Rho (Miro) GTPases localize to the outer mitochondrial membrane and are essential machinery for the regulated trafficking of mitochondria to defined subcellular locations. However, their sub-mitochondrial localization and relationship with other critical mitochondrial complexes remains poorly understood. Here, using super-resolution fluorescence microscopy, we report that Miro proteins form nanometer-sized clusters along the mitochondrial outer membrane in association with the Mitochondrial Contact Site and Cristae Organizing System (MICOS). Using knockout mouse embryonic fibroblasts we show that Miro1 and Miro2 are required for normal mitochondrial cristae architecture and Endoplasmic Reticulum-Mitochondria Contacts Sites (ERMCS). Further, we show that Miro couples MICOS to TRAK motor protein adaptors to ensure the concerted transport of the two mitochondrial membranes and the correct distribution of cristae on the mitochondrial membrane. The Miro nanoscale organization, association with MICOS complex and regulation of ERMCS reveal new levels of control of the Miro GTPases on mitochondrial functionality.

Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition.

Altered excitatory/inhibitory (E/I) balance is implicated in neuropsychiatric and neurodevelopmental disorders, but the underlying genetic etiology remains poorly understood. Copy number variations in CYFIP1 are associated with autism, schizophrenia, and intellectual disability, but its role in regulating synaptic inhibition or E/I balance remains unclear. We show that CYFIP1, and the paralog CYFIP2, are enriched at inhibitory postsynaptic sites. While CYFIP1 or CYFIP2 upregulation increases excitatory synapse number and the frequency of miniature excitatory postsynaptic currents (mEPSCs), it has the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Contrary to CYFIP1 upregulation, its loss in vivo, upon conditional knockout in neocortical principal cells, increases expression of postsynaptic GABAA receptor ß2/3-subunits and neuroligin 3, enhancing synaptic inhibition. Thus, CYFIP1 dosage can bi-directionally impact inhibitory synaptic structure and function, potentially leading to altered E/I balance and circuit dysfunction in CYFIP1-associated neurological disorders.

Tomato Juice Supplementation Influences the Gene Expression Related to Steatosis in Rats.

The objective of this work was to identify the effect of tomato juice on the expression of genes and levels of metabolites related to steatosis in rats. Male Sprague Dawley rats (8 weeks-old) were grouped (6 rats/group) in four experimental groups: NA (normal diet and water), NL (normal diet and tomato juice), HA (high-fat diet and water), and HL (high-fat diet and tomato juice). After an intervention period of 5 weeks, rats were sacrificed and biochemical parameters, biomarkers of oxidative stress, liver metabolites, and gene expression were determined. Although the H diet provoked dislipemia related to steatosis, no changes in isoprostanes or liver malondialdehyde (MDA) were observed. Changes in the gene expression of the HA group were produced by the high consumption of fat, whereas the consumption of tomato juice had different effects, depending on the diet. In the NL group, the genes involved in ß-oxidation were upregulated, and in groups NL and HL upregulation of CD36 and downregulation of APOB and LPL were observed. In addition, in the HL group the accumulation of lycopene upregulated the genes FXR and HNF4A, which have been suggested as preventive factors in relation to steatosis. Regarding the metabolomics study, intake of tomato juice stimulated the biosynthesis of glutathione and amino acids of the transulfurization pathway, increasing the levels of metabolites related to the antioxidant response.

Miro proteins coordinate microtubule- and actin-dependent mitochondrial transport and distribution.

In the current model of mitochondrial trafficking, Miro1 and Miro2 Rho-GTPases regulate mitochondrial transport along microtubules by linking mitochondria to kinesin and dynein motors. By generating Miro1/2 double-knockout mouse embryos and single- and double-knockout embryonic fibroblasts, we demonstrate the essential and non-redundant roles of Miro proteins for embryonic development and subcellular mitochondrial distribution. Unexpectedly, the TRAK1 and TRAK2 motor protein adaptors can still localise to the outer mitochondrial membrane to drive anterograde mitochondrial motility in Miro1/2 double-knockout cells. In contrast, we show that TRAK2-mediated retrograde mitochondrial transport is Miro1-dependent. Interestingly, we find that Miro is critical for recruiting and stabilising the mitochondrial myosin Myo19 on the mitochondria for coupling mitochondria to the actin cytoskeleton. Moreover, Miro depletion during PINK1/Parkin-dependent mitophagy can also drive a loss of mitochondrial Myo19 upon mitochondrial damage. Finally, aberrant positioning of mitochondria in Miro1/2 double-knockout cells leads to disruption of correct mitochondrial segregation during mitosis. Thus, Miro proteins can fine-tune actin- and tubulin-dependent mitochondrial motility and positioning, to regulate key cellular functions such as cell proliferation.

An Essential Role for the Tetraspanin LHFPL4 in the Cell-Type-Specific Targeting and Clustering of Synaptic GABAA Receptors.

Inhibitory synaptic transmission requires the targeting and stabilization of GABAA receptors (GABAARs) at synapses. The mechanisms responsible remain poorly understood, and roles for transmembrane accessory proteins have not been established. Using molecular, imaging, and electrophysiological approaches, we identify the tetraspanin LHFPL4 as a critical regulator of postsynaptic GABAAR clustering in hippocampal pyramidal neurons. LHFPL4 interacts tightly with GABAAR subunits and is selectively enriched at inhibitory synapses. In LHFPL4 knockout mice, there is a dramatic cell-type-specific reduction in GABAAR and gephyrin clusters and an accumulation of large intracellular gephyrin aggregates in vivo. While GABAARs are still trafficked to the neuronal surface in pyramidal neurons, they are no longer localized at synapses, resulting in a profound loss of fast inhibitory postsynaptic currents. Hippocampal interneuron currents remain unaffected. Our results establish LHFPL4 as a synapse-specific tetraspanin essential for inhibitory synapse function and provide fresh insights into the molecular make-up of inhibitory synapses.

Errores en el proceso de medicación de pacientes internados en el Hospital Público Materno Infantil de Salta / Errors in the Medication Process of Inpatients at Hospital Público Materno Infantil de Salta

INTRODUCCIÓN: Los errores de medicación son causa de eventos adversos durante el proceso asistencial. OBJETIVOS: Caracterizar los errores en el proceso de medicación del Hospital Público Materno Infantil de Salta. MÉTODOS: Los errores fueron identificados a partir de la validación farmacéutica de las prescripciones. Se calcularon las tasas de error, y se analizó su asociación con factores del paciente, del tratamiento farmacológico y del recurso humano. RESULTADOS: Entre el 1 de noviembre de 2012 y el 31 de enero de 2013 se validaron 18 203 prescripciones, en las que se detectaron 2989 (96,7%) errores de prescripción, 79 (2,5%) de administración, 6 (0,2%) de transcripción y 18 (0,6%) de dispensa. La tasa de error del Área Perinatológica fue de 13,06 cada 100 días-paciente; se destacaron la omisión de dosis (30%) y la prescripción de dosis incorrecta (23%). En el Área Pediátrica la tasa fue de 8,6 cada 100 días-paciente, con 55% de prescripción de dosis incorrecta, asociada a la edad del niño. Los grupos farmacoterapéuticos involucrados fueron: analgésicos antiinflamatorios no esteroideos, drogas del aparato digestivo y circulatorio, y antiinfecciosos. La mayor parte de los errores se produjo con drogas de uso habitual, con consecuencias potencialmente significativas para los pacientes. La tasa de error fue similar para médicos en formación y de planta. CONCLUSIONES: La farmacovigilancia intensiva permitió identificar un número elevado de errores, cuya caracterización es útil para implementar estrategias de prevención.

INTRODUCTION: Medication errors cause adverse events in health care. OBJECTIVES: To characterize the medication process errors at Hospital Materno Infantil of Salta. METHODS: Errors were identified by pharmaceutical validation of prescriptions. Error rates were calculated, and associations between error and patient factors, drug treatment and human resource were determined. RESULTS: From November 1, 2012 to January 31, 2013 a total of 18 203 prescriptions were validated, identifying 2 989 (96.7%) errors of prescription, 79 (2.5%) of administration, 6 (0.2%) of transcription and 18 (0.6%) of dispensing. The error rate was 13.06 per 100 patient days for the Perinatology Area, with 30% of omission of doses and 23% of incorrect dose prescription. In the Pediatric Area, the rate was 8.6 per 100 patient days, with 55% of wrong doses, associated with child age. The pharmacotherapeutic groups involved were: non-steroidal anti-inflammatory drugs, digestive and circulatory system drugs, and anti-infectives. Most errors occurred with commonly used drugs, with potentially significant consequences for patients. The error rate was similar to doctors in training and permanent staff. CONCLUSIONS: Intensive pharmacovigilance allowed the identification of a large number of errors. Their characterization will permit to establish prevention strategies.

Loss of Dendritic Complexity Precedes Neurodegeneration in a Mouse Model with Disrupted Mitochondrial Distribution in Mature Dendrites.

Correct mitochondrial distribution is critical for satisfying local energy demands and calcium buffering requirements and supporting key cellular processes. The mitochondrially targeted proteins Miro1 and Miro2 are important components of the mitochondrial transport machinery, but their specific roles in neuronal development, maintenance, and survival remain poorly understood. Using mouse knockout strategies, we demonstrate that Miro1, as opposed to Miro2, is the primary regulator of mitochondrial transport in both axons and dendrites. Miro1 deletion leads to depletion of mitochondria from distal dendrites but not axons, accompanied by a marked reduction in dendritic complexity. Disrupting postnatal mitochondrial distribution in vivo by deleting Miro1 in mature neurons causes a progressive loss of distal dendrites and compromises neuronal survival. Thus, the local availability of mitochondrial mass is critical for generating and sustaining dendritic arbors, and disruption of mitochondrial distribution in mature neurons is associated with neurodegeneration.

Pobres / Poor

La medicina es una riquísima experiencia de vida. Relaciona a personas plenas de incertidumbres temor, dolor, en trances difíciles y a veces, mortales. Recuerdos y vivencias cotidianas enseñan, duelen, obligan a recapacitar. Un pediatra salteño, docente de buena pluma comparte recuerdos. Dice: "Pedro Martínez no se llama así. Existió en una historia similar a la que cuento y participé de ella. Casi treinta años después, me sigue acompañando y reaparece cada vez que corro el riesgo de olvidarme que no todos la pasamos bien en el mundo…".Su blog www.baleromedico.wordpress.com ofrece muchas otras acuarelas plenas de visiones tiernas que en su conjunto rememoran al "Corazón"de Edmundo De Amicis (Italia, 1846-1908).

Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling.

It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca(2+). Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca(2+)-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca(2+) in astrocytic processes. Thus, the regulation of intracellular Ca(2+) signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca(2+) wave propagation, gliotransmission, and ultimately neuronal function.

Mitochondrial trafficking in neurons and the role of the Miro family of GTPase proteins.

Correct mitochondrial dynamics are essential to neuronal function. These dynamics include mitochondrial trafficking and quality-control systems that maintain a precisely distributed and healthy mitochondrial network, so that local energy demands or Ca2+-buffering requirements within the intricate architecture of the neuron can be met. Mitochondria make use of molecular machinery that couples these organelles to microtubule-based transport via kinesin and dynein motors, facilitating the required long-range movements. These motors in turn are associated with a variety of adaptor proteins allowing additional regulation of the complex dynamics demonstrated by these organelles. Over recent years, a number of new motor and adaptor proteins have been added to a growing list of components implicated in mitochondrial trafficking and distribution. Yet, there are major questions that remain to be addressed about the regulation of mitochondrial transport complexes. One of the core components of this machinery, the mitochondrial Rho GTPases Miro1 (mitochondrial Rho 1) and Miro2 have received special attention due to their Ca2+-sensing and GTPase abilities, marking Miro an exceptional candidate for co-ordinating mitochondrial dynamics and intracellular signalling pathways. In the present paper, we discuss the wealth of literature regarding Miro-mediated mitochondrial transport in neurons and recently highlighted involvement of Miro proteins in mitochondrial turnover, emerging as a key process affected in neurodegeneration.