Nektarios Tavernarakis

Foundation for Research and Technology - Hellas | forth · Institute of Molecular Biology and Biotechnology (IMBB)

The mTORC1 nutrient-sensing pathway integrates metabolic and endocrine signals into the brain to evoke physiological responses to food deprivation, such as autophagy. Nevertheless, the impact of neuronal mTORC1 activity on neuronal circuits and organismal metabolism remains obscure. Here, we show that mTORC1 inhibition acutely perturbs serotonergic...

Mitochondria are central regulators of healthspan and lifespan, yet the intricate choreography of multiple, tightly controlled steps regulating mitochondrial biogenesis remains poorly understood. Here, we uncover a pivotal role for specific elements of the 5'-3' mRNA degradation pathway in the regulation of mitochondrial abundance and function. We...

Neurons are highly polarized, post-mitotic cells that are characterized by unique morphological diversity and complexity. As highly differentiated cells that need to survive throughout organismal lifespan, neurons face exceptional energy challenges in time and space. Therefore, neurons are heavily dependent on a healthy mitochondrial network for th...

Since its introduction by Sydney Brenner, Caenorhabditis elegans has become a widely studied organism. Given its highly significant properties, including transparency, short lifespan, self-fertilization, high reproductive yield and ease in manipulation and genetic modifications, the nematode has contributed to the elucidation of several fundamental...

The nervous system participates in the initiation and modulation of systemic stress. Ionstasis is of utmost importance for neuronal function. Imbalance in neuronal sodium homeostasis is associated with pathologies of the nervous system. However, the effects of stress on neuronal Na+ homeostasis, excitability, and survival remain unclear. We report...

Systemic control of homeostatic processes is of fundamental importance for survival and adaptation in metazoans. In this issue of Cell Metabolism, Chen and colleagues identify and methodically dissect a signaling cascade that is mobilized by the agouti-related peptide (AgRP)-expressing neurons in the hypothalamus, to ultimately modulate autophagy a...

Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiolo...

Here, we present an olfactory-dependent chemotaxis assay for evaluating changes in memory-like behavior in both wild-type and Alzheimer's-disease-like C. elegans models. We describe steps for synchronizing and preparing C. elegans populations and for performing isoamyl alcohol conditioning during starvation and chemotaxis assaying. We then detail c...

SNARE proteins reside between opposing membranes and facilitate vesicle fusion, a physiological process ubiquitously required for secretion, endocytosis and autophagy. With age, neurosecretory SNARE activity drops and is pertinent to age-associated neurological disorders. Despite the importance of SNARE complex assembly and disassembly in membrane...

Mitochondria preserve metabolic homeostasis and integrate stress signals, to trigger cytoprotective, or cell death pathways. Mitochondrial homeostasis and function decline with age. The mechanisms underlying the deterioration of mitochondrial homeostasis during ageing, or in age-associated pathologies, remain unclear. Here, we show that CISD-1, a m...

Aging is the major risk factor for several life-threatening pathologies and impairs the function of multiple cellular compartments and organelles. Age-dependent deterioration of nuclear morphology is a common feature in evolutionarily divergent organisms. Lipid droplets have been shown to localize in most nuclear compartments, where they impinge on...

Mitochondria hold diverse and pivotal roles in fundamental processes that govern cell survival, differentiation, and death, in addition to organismal growth, maintenance, and aging. The mitochondrial protein import system is a major contributor to mitochondrial biogenesis and lies at the crossroads between mitochondrial and cellular homeostasis. Re...

Reactive oxygen species (ROS) have been described to induce a broad range of redox-dependent signaling reactions in physiological conditions. Nevertheless, an excessive accumulation of ROS leads to oxidative stress, which was traditionally considered as detrimental for cells and organisms, due to the oxidative damage they cause to biomolecules. Dur...

After three decades of extensive research on the molecular biology of aging, we can now specify several molecular and cellular processes that accelerate or delay aging in animal model systems. Molecular mechanisms that affect metabolism, caloric and dietary consumption, genomic stability, telomere attrition, autophagy and epigenetic alterations are...

Marked alterations in nuclear ultrastructure are a universal hallmark of aging, progeroid syndromes and other age-related pathologies. Here we show that autophagy of nuclear proteins is an important determinant of fertility and aging. Impairment of nucleophagy diminishes stress resistance, germline immortality and longevity. We found that the nemat...

Autophagy is a physiological response, activated by a myriad of endogenous and exogenous cues, including DNA damage, perturbation of proteostasis, depletion of nutrients or oxygen and pathogen infection. Upon sensing those stimuli, cells employ multiple non-selective and selective autophagy pathways to promote fitness and survival. Importantly, the...

Proteome integrity is a prerequisite for cellular functionality and organismal viability. Its compromise is considered an inherent part of the aging process and has been associated with the onset of age-related, neurodegenerative pathologies. Although the molecular underpinnings of protein homeostasis (proteostasis) have been extensively studied, s...

Life expectancy in Western countries is increasing, with concomitant rise in ageing-related pathologies, including Parkinson’s and Alzheimer’s disease, as well as other neurodegenerative diseases. Consequently, the medical, psychological and economic burden to society is increasing. Thus, understanding the cellular and molecular mechanisms underlyi...

Transgenic Caenorhabditis elegans that expresses the full-length wild-type human α-synuclein in dopaminergic neurons provides a well-established Parkinson’s disease (PD) nematode model. Here, we present a detailed protocol to monitor and dissect the molecular underpinnings of age-associated neurodegeneration using this PD nematode model. This proto...

Sustained mitochondrial fitness relies on coordinated biogenesis and clearance. Both processes are regulated by constant targeting of proteins into the organelle. Thus, mitochondrial protein import sets the pace for mitochondrial abundance and function. However, our understanding of mitochondrial protein translocation as a regulator of longevity re...

Autophagy is a universal cellular homeostatic process, required for the clearance of dysfunctional macromolecules or organelles. This self-digestion mechanism modulates cell survival, either directly by targeting cell death players, or indirectly by maintaining cellular balance and bioenergetics. Nevertheless, under acute or accumulated stress, aut...

One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to various biosynthetic pathways. The folate cycle and methionine cycle are the two key modules of this network that regulate purine and thymidine synthesis, amino acid homeostasis, and epigenetic mechanisms. Intersection with the transsulfuration pathway...

Nucleophagy is an organelle-selective subtype of autophagy that targets nuclear material for degradation. The macroautophagic delivery of micronuclei to the vacuole, together with the nucleus-vacuole junction-dependent microautophagic degradation of nuclear material, were first observed in yeast. Nuclear pore complexes and ribosomal DNA are typical...

The nematode Caenorhabditis elegans is a powerful experimental platform for cell biology studies. The molecular mechanisms that mediate cell death and neurodegeneration have been characterized extensively in the nematode. In addition, the availability of a wide arsenal of genetic and molecular tools and methodologies renders C. elegans an organism...

Ageing in diverse species ranging from the simple nematode Caenorhabditis elegans to humans is associated with a marked decrease of neuronal function and increased susceptibility to neurodegeneration. Accumulating findings also indicate that alterations in neuronal functionality with age are associated with a decline in mitochondrial integrity and...

In evolutionary distant organisms, like yeast and mammals, the endoplasmic reticulum (ER) and mitochondria retain a unique composition of phospholipids and proteins to maintain organelle structure and function. Organellar phospholipid biosynthesis and remodeling are essential for protein synthesis, folding and secretion. Notably, proteotoxic and ph...

In this special interview series, we profile members of The FEBS Journal editorial board to highlight their research focus, perspectives on the journal and future directions in their field. Nektarios Tavernarakis is Chairman of the Board of Directors at the Foundation for Research and Technology‐Hellas (FORTH), and Professor of Molecular Systems Bi...

Aging, genomic stress, and mitochondrial dysfunction are risk factors for neurodegenerative pathologies, such as Parkinson disease (PD). Although genomic instability is associated with aging and mitochondrial impairment, the underlying mechanisms are poorly understood. Here, we show that base excision repair generates genomic stress, promoting age-...

Progressive accumulation of damaged cellular constituents contributes to age-related diseases. Autophagy is the main catabolic process, which recycles cellular material in a multitude of tissues and organs. Autophagy is activated upon nutrient deprivation, and oncogenic, heat or oxidative stress-induced stimuli to selectively degrade cell constitue...

Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discu...

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, agi...

Mitochondrial dysfunction and mitophagy are often hallmarks of neurodegenerative diseases such as autosomal dominant optic atrophy (ADOA) caused by mutations in the key mitochondrial dynamics protein optic atrophy 1 (Opa1). However, the second messengers linking mitochondrial dysfunction to initiation of mitophagy remain poorly characterized. Here,...

The in‐vivo elucidation of the molecular mechanisms underlying muscles dysfunction due to aging via non‐invasive label free imaging techniques is an important issue with high biological significance. In the present study, polarization‐dependent second‐harmonic generation (PSHG) was used to evaluate structural alterations in the striated muscles dur...

The incidence and prognosis of clonal hematopoiesis in patients with isolated neutropenia among patients with idiopathic cytopenia of undetermined significance (ICUS), known as ICUS-N or chronic idiopathic neutropenia (CIN) patients, is poorly defined. In the present study we sought to investigate the frequency and clinical significance of mutation...

Autophagy is an evolutionarily conserved degradation process maintaining cell homeostasis. Induction of autophagy is triggered as a response to a broad range of cellular stress conditions, such as nutrient deprivation, protein aggregation, organelle damage and pathogen invasion. Macroautophagy involves the sequestration of cytoplasmic contents in a...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, senescent decline and ageing is broadly influenced by genetic and extrinsic factors. Numerous gene mutations and treatments have been shown to extend the li...

Autophagy is a well-conserved self-degrading mechanism, which involves the elimination of unnecessary or damaged cellular constituents. Although extensively studied, many aspects regarding its tight regulation and its implication in health and disease remain elusive. The nematode Caenorhabditis elegans has been widely used as a simple multicellular...

Autophagy is the main catabolic process by which cells recycle cytoplasmic components and superfluous or damaged organelles to preserve metabolic homeostasis under normal conditions and promote survival under stress. As a tightly regulated and dynamic process, autophagy has critical roles in development and cell differentiation, immune function, or...

The insulin/IGF signalling pathway impacts lifespan across distant taxa, by controlling the activity of nodal transcription factors. In the nematode Caenorhabditis elegans, the transcription regulators DAF-16/FOXO and SKN-1/Nrf function to promote longevity under conditions of low insulin/IGF signalling and stress. The activity and subcellular loca...

Maintaining a healthy proteome is essential for cell and organismal homeostasis. Perturbation of the balance between protein translational control and degradation instigates a multitude of age-related diseases. Decline of proteostasis quality control mechanisms is a hallmark of ageing. Biochemical methods to detect de novo protein synthesis are sti...

Mitochondrial biogenesis is indispensable for organismal homeostasis. The semi-autonomous nature of mitochondria makes their biogenesis rather complex, as it requires the contribution of the nucleus, the cytoplasm and the organelle itself. Recently, several transcription regulators, RNA binding proteins and outer mitochondrial membrane (OMM) compon...

In autosomal dominant optic atrophy (ADOA), caused by mutations in the mitochondrial cristae biogenesis and fusion protein optic atrophy 1 (Opa1), retinal ganglion cell (RGC) dysfunction and visual loss occur by unknown mechanisms. Here, we show a role for autophagy in ADOA pathogenesis. In RGCs expressing mutated Opa1, active 5’ AMP-activated prot...

A vicious cycle, linking obesity with chronic inflammation, fuels the development and exacerbation of metabolic syndrome and other disorders. Modulation of mitochondrial energy metabolism via interleukin-1β signaling establishes a runaway positive-feedback loop that brings about and reinforces the sequelae of a high-fat diet.

Multiple sclerosis (MS) is an autoimmune life-threatening disease, afflicting millions of people worldwide. Although the disease is non-curable, considerable therapeutic advances have been achieved through molecular immunotherapeutic approaches, such as peptides vaccination, administration of monoclonal antibodies, and immunogenic copolymers. The m...

Ageing is driven by the inexorable and stochastic accumulation of damage in biomolecules vital for proper cellular function. Although this process is fundamentally haphazard and uncontrollable, genetic and extrinsic factors influence senescent decline and ageing. Numerous gene mutations and treatments have been shown to extend the lifespan of organ...

Females and males differ substantially in various neuronal functions in divergent, sexually dimorphic animal species, including humans. Despite its developmental, physiological and medical significance, understanding the molecular mechanisms by which sex-specific differences in the anatomy and operation of the nervous system are established remains...

Imbalance between the main intracellular degradative, trafficking and intercellular shuttling pathways has been implicated in disease pathogenesis. Autophagy controls degradation of cellular components, while vesicular trafficking permits transport of material in and out of the cell. Emerging evidence has uncovered the extensive interconnectivity b...

The in-depth study of protein–protein interactions (PPIs) is of key importance for understanding how cells operate. Therefore, in the past few years, many experimental as well as computational approaches have been developed for the identification and discovery of such interactions. Here, we present UniReD, a user-friendly, computational prediction...

Human civilization is unique with respect to the organization of our natural environment, allowing constant supply of nutrients to most individuals in developed countries, contrasting with the natural fluctuation in food sources found in wildlife. Indeed, scarcity of nutrients has been a continuous threat for most living organisms, thus leading to...

Maintenance of synaptic homeostasis is a challenging task, due to the intricate spatial organization and intense activity of synapses. Typically, synapses are located far away from the neuronal cell body, where they orchestrate neuronal signalling and communication, through neurotransmitter release. Stationary mitochondria provide energy required f...

The nematode Caenorhabditis elegans offers unique advantages that enable a comprehensive delineation of the cellular and molecular mechanisms underlying devastating human pathologies such as stroke, ischemia and age-associated neurodegenerative disorders. Genetic models of human diseases that closely simulate several disease-related phenotypes have...

Recently, we reported that, in mice, hunger causes the autophagy-dependent release of a protein called “acyl-CoA-binding protein” or “diazepam binding inhibitor” (ACBP/DBI) from cells, resulting in an increase in plasma ACBP concentrations. Administration of extra ACBP is orexigenic and obesogenic, while its neutralization is anorexigenic in mice,...

The cover image is based on the Short Communication Synaptic vesicle fusion is modulated through feedback inhibition by dopamine auto‐receptors by Rosaria Formisano et al., DOI 10.1002/syn.22131.

Model for fine-tuning synaptic dopamine levels at dopaminergic synapses where DOP-2, DAT-1 and ASIC-1 form a modulatory hub. Fusion of acidified neurotransmitter vesicles with the synaptic membrane causes release of dopamine and H+ ions. Dopamine activates a feedback loop through auto-receptors (DOP-2), and possibly through the membrane transporter...

Nuclear recycling is essential for cell and organismal homeostasis. Nuclear architecture perturbations, such as nuclear loss or nuclear enlargement, have been observed in several pathological conditions. Apart from proteasomal components which reside in the nucleus, specific autophagic proteins also shuttle between the nucleus and the cytoplasm. Un...

Autophagy is crucial for neuronal integrity. Loss of key autophagic components leads to progressive neurodegeneration and structural defects in neuronal synapses. However, the molecular mechanisms regulating autophagy in the brain remain elusive. Similarly, while it is widely accepted that protein turnover is required for synaptic plasticity, the c...

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were...

Caloric restriction mimetics (CRMs) are natural or synthetic compounds that mimic the health-promoting and longevity-extending effects of caloric restriction. CRMs provoke the deacetylation of cellular proteins coupled to an increase in autophagic flux in the absence of toxicity. Here, we report the identification of a novel candidate CRM, namely 3...

Signals emanating from the nervous system are potent modulators of longevity. It now seems that overall neural excitation is also a key determinant of lifespan. Reducing neuronal excitation increases lifespan across species.

The term lipophagy is used to describe the autophagic degradation of lipid droplets, the main lipid storage organelles of eukaryotic cells. Ever since its discovery in 2009, lipophagy has emerged as a significant component of lipid metabolism with important implications for organismal health. This review aims to provide a brief summary of our curre...

The cytoskeleton consists of filamentous protein polymers that form organized structures, contributing to a multitude of cell life aspects. It includes three types of polymers: the actin microfilaments, the microtubules and the intermediate filaments. Decades of research have implicated the cytoskeleton in processes that regulate cellular and organ...

Posttranslational modifications are ubiquitous regulators of cellular processes. The regulatory role of SUMOylation, the attachment of a small ubiquitin-related modifier to a target protein, has been implicated in fundamental processes like cell division, DNA damage repair, mitochondrial homeostasis, and stress responses. Recently, it is gaining mo...

Autophagy facilitates the adaptation to nutritional stress. Here, we show that short-term starvation of cultured cells or mice caused the autophagy-dependent cellular release of acyl-CoA-binding protein (ACBP, also known as diazepam-binding inhibitor, DBI) and consequent ACBP-mediated feedback inhibition of autophagy. Importantly, ACBP levels were...

Mitochondrial respiratory states and rates MitoEAGLE Task Group

Neurodegenerative diseases are strongly age-related and currently cannot be cured, with a surge of patient numbers in the coming decades in view of the emerging worldwide ageing population, bringing healthcare and socioeconomic challenges. Effective therapies are urgently needed, and are dependent on new aetiological mechanisms. In neurons, efficie...

The C. elegans germline recapitulates mammalian stem cell niches and provides an effective platform for investigating key aspects of stem cell biology. However, the molecular and physiological requirements for germline stem cell homeostasis remain largely elusive. Here, we report that mitochondrial biogenesis and function are crucial for germline s...