Neurons rely on localized mitochondria to fulfill spatially heterogeneous metabolic demands. Mitochondrial aging occurs on timescales shorter than the neuronal lifespan, necessitating transport of fresh material from the soma. Maintaining an optimal distribution of healthy mitochondria requires an interplay between a stationary pool localized to sites of high metabolic demand and a motile pool capable of delivering new material. Interchange between these pools can occur via transient fusion / fission events or by halting and restarting entire mitochondria. Our quantitative model of neuronal mitostasis identifies key parameters that govern steady-state mitochondrial health at discrete locations. Very infrequent exchange between stationary and motile pools optimizes this system. Exchange via transient fusion allows for robust maintenance, which can be further improved by selective recycling through mitophagy. These results provide a framework for quantifying how perturbations in organelle transport and interactions affect mitochondrial homeostasis in neurons, a key aspect underlying many neurodegenerative disorders.
Cell and tissue functions rely on an elaborate intracellular transport system responsible for distributing bioactive molecules with high spatiotemporal accuracy. The tubular network of the Endoplasmic Reticulum (ER) constitutes a system for the delivery of luminal solutes it stores, including Ca2+, across the cell periphery. The physical nature and factors underlying the ER's functioning as a fluidics system are unclear. Using an improved ER transport visualisation methodology combined with optogenetic Ca2+ dynamics imaging, we observed that ER luminal transport is modulated by natural ER tubule narrowing and dilation, directly proportional to the amount of an ER membrane morphogen, Reticulon 4 (RTN4). Consequently, the ER morphoregulatory effect of RTN4 defines ER's capacity for peripheral Ca2+ delivery and thus controls axonogenesis. Excess RTN4 limited ER luminal transport, Ca2+ release and iPSC-derived cortical neurons' axonal extension, while RTN4 elimination reversed the effects.
In this paper, we describe an improved technique for using the backscattered phase from meteor radar echo measurements just prior to the specular point (t 0) to calculate meteor speeds and their uncertainty. Our method, which builds on earlier work of Cervera et al. (1997, https://doi.org/10.1029/ 96RS03638), scans possible speeds in the Fresnel distance-time domain with a dynamic, sliding window and derives a best-speed estimate from the resultant speed distribution. We test the performance of our method, called pre-t 0 speeds by sliding-slopes technique (PSSST), on transverse scattered meteor echoes observed by the Middle Atmosphere Alomar Radar System (MAARSY) and the Canadian Meteor Orbit Radar (CMOR) and compare the results to time-of-flight and Fresnel transform speed estimates. Our novel technique is shown to produce good results when compared to both model and speed measurements using other techniques. We show that our speed precision is ±5% at speeds less than 40 km/s, and we find that more than 90% of all CMOR multistation echoes have PSSST solutions. For CMOR data, PSSST is robust against the selection of critical phase value and poor phase unwrapping. Pick errors of up to ±6 pulses for meteor speeds less than about 50 km/s produce errors of less than ±5% of the meteoroid speed. In addition, the width of the PSSST speed Kernel density estimate (KDE) is used as a natural measure of uncertainty that captures both noise and t 0 pick uncertainties.
Eukaryotic cells modulate their metabolism by organizing metabolic components in response to varying nutrient availability and energy demands. In rat axons, mitochondria respond to glucose levels by halting active transport in high glucose regions. We employ quantitative modeling to explore physical limits on spatial organization of mitochondria and localized metabolic enhancement through regulated stopping of processive motion. We delineate the role of key parameters, including cellular glucose uptake and consumption rates, that are expected to modulate mitochondrial distribution and metabolic response in spatially varying glucose conditions. Our estimates indicate that physiological brain glucose levels fall within the limited range necessary for metabolic enhancement. Hence mitochondrial localization is shown to be a plausible regulatory mechanism for neuronal metabolic flexibility in the presence of spatially heterogeneous glucose, as may occur in long processes of projection neurons. These findings provide a framework for the control of cellular bioenergetics through organelle trafficking.
Mitochondria are critical for neuronal function and must be reliably distributed through complex neuronal architectures. By quantifying in vivo mitochondrial transport and localization patterns in the dendrites of Drosophila visual system neurons, we show that mitochondria make up a dynamic system at steady-state, with significant transport of individual mitochondria within a stable global pattern. Mitochondrial motility patterns are unaffected by visual input, suggesting that neuronal activity does not directly regulate mitochondrial localization in vivo. Instead, we present a mathematical model in which four simple scaling rules enable the robust self-organization of the mitochondrial population. Experimental measurements of dendrite morphology validate key model predictions: to maintain equitable distribution of mitochondria across asymmetrically branched subtrees, dendritic branch points obey a parent-daughter power law that preserves cross-sectional area, and thicker trunks support proportionally bushier subtrees. Altogether, we propose that ″housekeeping″ requirements, including the need to maintain steady-state mitochondrial distributions, impose constraints on neuronal architecture.
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