Mitochondria

Support experimental research on delivering nucleic acids into mitochondria in Ben Luisi’s laboratory, supervised by Pedro Rebelo-Guiomar. The role develops delivery methods in an interactive biochemistry research group. Funding is available from 15 January to 5 December 2027 in the first instance.

…They discuss photobiomodulation, mitochondria, collagen and the limitations of available studies, alongside the distinction between regulatory clearance and evidence for a particular consumer device.

Parkinson's disease (PD), characterized by the absence of dopamine in the striatum[1], is caused by the death of the substantia nigra pars compacta dopamine (SNcDA) neurons in the midbrain. The loss of these autonomously pacemaking[2] neurons is attributed to irreparable damage due to a dysregulation cascade starting from excess cytosolic dopamine and its decomposition into its aldehyde[3]. However, it is unresolved if dopamine dysregulation in SNcDA neurons themselves is the cause of PD or if it is a mere symptom. Here, we applied a recent theory of metabolic spikes[4] to SNcDA neurons, to

…known to locate and accumulate in the mitochondria.Research has demonstrated that nuclear transcription factors(nTF) play a direct or indirect role in the transcriptional regulation of mitochondria, which lose function in the early stages of neurodegenerative diseases.Based on this information, our study investigates the interactions between Aβ and nTFs in mitochondria.In this study, the interaction of 48 nTFs with Aβ was examined using a nTF-interaction kit. Mitochondrial lysate isolations were per

Background: Emerging evidence suggests a central role of mitochondria in psychiatric disorders. We have previously shown that high anxious (HA) rats exhibit reduced active coping behavior under adversity and competitiveness. HA animals also show alterations in the neural circuits involved in motivation such as nucleus accumbens (Nac), at both the cellular and organelle level. We have identified an essential role for mitochondria and energy metabolism in NAc function in effort-related and motivated behaviors, suggesting that boosting mitochondrial function in the NAc could lead to enhanced perf

Mitochondria play a crucial role in cellular energy production. Dysfunctional mitochondria have been causally linked to a myriad of age-related disorders, including neurodegenerative diseases. We recently discovered Zinc finger CCCH-type containing 10 (Zc3h10) as a novel mitochondrial regulator in adipocytes and muscle cells. Since neuronal maturation is the phase during which neurons acquire their final characteristics in terms of morphology, electrical activity, and metabolism, and given the high expression level of Zc3h10 in various brain areas, we decided to investigate the role of this mi

Parkinson’s disease (PD), characterized by the absence of dopamine in the striatum, is due to the death of the substantia nigra pars compacta dopamine (SNcDA) neurons in the midbrain. This cell loss is attributed to a dysregulation cascade originating from excess cytosolic dopamine. This presents a paradox. Why is the cytosolic dopamine, while available and in excess, not being released into the striatum and instead causing cell death? Here, we apply our recent theory wherein neurons self-initiate action potentials to maintain metabolic homeostasis. We propose that in PD, such metabolically re

…H2O2, HyPer7 was expressed in the mitochondria of either astrocytes

Arginase 2 (Arg2), an arginine-metabolizing, mitochondrial enzyme, has been recently found to be enriched in the striatum, and progressive loss of Arg2 has been proposed as a potential factor contributing to the pathogenesis of Huntington’s disease (HD), a disorder primarily involving this region of the brain. Although direct metabolic role of Arg2 is well established, the importance of this enzyme for striatal function and dysfunction is not known. The purpose of this work was to identify cellular pathways potentially controlled by Arg2 in the striatum. In our experiments, we have used wild-t

…which requires highly functional mitochondria. Previous studies have shown dysregulations of mitochondria within the hippocampus (HPC) are apparent early on in cases of Alzheimer’s Disease (AD), even preceding the major pathological hallmarks: tau aggregation, amyloid-beta plaques, and impairments in memory. Optogenetic tools have

Form and function of neurons are intricately linked. Long axons reach far away targets and dendrites branch wide to integrate signals, allowing neurons to form an extremely dense network to process external stimuli. While we are gaining a better understanding of the rules of circuit wiring, at the intracellular level we still lack an understanding about which features are random, which are controlled organization and which are cell type specific. Reconstructions of the neuronal ultrastructure is a multiscale problem spanning from the few nm-scale of ER diameter to the dimension of cells and ne

Neurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion over long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons’ possess this capacity, but ultrastructural data over substantial portions of a neuron’s extent that would allow for tests of such hypotheses are scarce. Here, we mined the Caenorhabditis

Parkinson's disease (PD), characterized by the absence of dopamine in the striatum[1], is caused by the death of the substantia nigra pars compacta dopamine (SNcDA) neurons in the mid-brain. The cause of this cell loss is attributed to irreparable damage due to a dysregulation cascade originating from excess cytosolic dopamine[2]. However, it is unresolved if dopamine dysregulation in SNcDA neurons themselves is the cause of PD or if it is a mere symptom. Here, we introduce a theory of specialized non-causal action potentials that serve metabolic homeostasis called `metabolic spikes' which can

…on the role of redox processes and mitochondria in the context of abnormal neuronal excitability associated with epilepsy. We have shown that that status epilepticus (SE) alters mitochondrial and cellular redox status, energetics and function and conversely, that reactive oxygen species and resultant dysfunction can lead to chronic epilepsy. Oxidative stress and neuroinflammatory pathways have considerable crosstalk and targeting redox processes has recently been sho

Maintaining average activity level within a set-point range constitutes a fundamental property of central neural circuits. Accumulated evidence suggests that firing rate distributions and their means represent physiological variables regulated by homeostatic systems during sleep-wake cycle in central neural circuits. While intracellular Ca2+ has long been hypothesized as a feedback control signal, the source of Ca2+ and the molecular machinery enabling network-wide homeostatic responses remain largely unknown. I will present our hypothesis and framework on identifying homeostatic regulators i

Neural circuit functions are stabilized by homeostatic mechanisms at long timescales in response to changes in experience and learning. However, we still do not know which specific physiological variables are being stabilized, nor which cellular or neural-network components comprise the homeostatic machinery. At this point, most evidence suggests that the distribution of firing rates amongst neurons in a brain circuit is the key variable that is maintained around a circuit-specific set-point value in a process called firing rate homeostasis. Here, I will discuss our recent findings that implic

In order to re-install neurogenesis after loss of neurons upon injury or neurodegeneration, we need to understand the basic principles of neurogenesis. I will first discuss about our discovery of a novel centrosome protein (Camargo et al., 2019) and discuss unpublished work about the great diversity of interphase centrosome proteomes and their relevance for neurodevelopmental disorders. I would then present work on a master regulator of neural stem cell amplification and brain folding (Stahl et al., 2013; Esgleas et al., 2020) to proceed presenting data on utilizing some of these factors for t

Spontaneous firing, observed in many neurons, is often attributed to ion channel or network level noise. Cortical cells during slow wave sleep exhibit transitions between so called Up and Down states. In this sleep state, with limited sensory stimuli, neurons fire in the Up state. Spontaneous firing is also observed in slices of cholinergic interneurons, cerebellar Purkinje cells and even brainstem inspiratory neurons. In such in vitro preparations, where the functional relevance is long lost, neurons continue to display a rich repertoire of firing properties. It is perplexing that these neuro