Mitochondria preserve metabolic homeostasis and integrate stress signals, to trigger cytoprotecti... more 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 mitochondrial iron-sulfur cluster binding protein, implicated in the pathogenesis of Wolfram neurodegenerative syndrome type 2, modulates longevity in the nematode Caenorhabditis elegans by engaging autophagy and the mitochondrial intrinsic apoptosis pathway. The anti-apoptotic protein CED-9 is the downstream effector that mediates CISD-1-dependent effects on proteostasis, neuronal integrity and lifespan. Moreover, intracellular iron abundance is critical for CISD-1 function, since mild iron supplementation is sufficient to decelerate ageing and partly ameliorate the disturbed mitochondrial bioenergetics and proteostasis of CISD-1 deficient...
Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite ... more Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite its crucial role in vital biological processes, exceeded iron levels can be harmful for cellular and organismal homeostasis, due to iron’s involvement in the generation of toxic hydroxyl radicals. As such, maintaining balanced iron levels is highly required in order for the organisms to avoid iron toxicity and at the same time preserve iron-dependent processes. This is achieved by the tight coordination of intricate systemic, cellular and subcellular mechanisms for iron absorption, excretion, utilization and storage. Those mechanisms decline during ageing, as well as in multiple human pathologies, leading to iron overload or deprivation, and eventually to death. To gain insight into how perturbations in iron homeostasis lead to disease, it is of great importance to use efficient methods for iron detection in distinct biological samples. Towards this direction, several biochemical and biophysical methods have been developed for the determination of iron and iron-containing compounds.
Autophagy is a universal cellular homeostatic process, required for the clearance of dysfunctiona... more 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, autophagy can also contribute to promote different modes of cell death, either through highly regulated signalling events, or in a more uncontrolled inflammatory manner. Conversely, apoptotic or necroptotic factors have also been implicated in the regulation of autophagy, while specific factors regulate both processes. Here, we survey both earlier and recent findings, highlighting the intricate interaction of autophagic and cell death pathways. We, Furthermore, discuss paradigms, where this cross-talk is disrupted, in the context of disease.
One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to ... more 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 supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and relate...
Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite ... more Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite its crucial role in vital biological processes, exceeded iron levels can be harmful for cellular and organismal homeostasis, due to iron’s involvement in the generation of toxic hydroxyl radicals. As such, maintaining balanced iron levels is highly required in order for the organisms to avoid iron toxicity and at the same time preserve iron-dependent processes. This is achieved by the tight coordination of intricate systemic, cellular and subcellular mechanisms for iron absorption, excretion, utilization and storage. Those mechanisms decline during ageing, as well as in multiple human pathologies, leading to iron overload or deprivation, and eventually to death. To gain insight into how perturbations in iron homeostasis lead to disease, it is of great importance to use efficient methods for iron detection in distinct biological samples. Towards this direction, several biochemical and bio...
Autophagy is a well-conserved self-degrading mechanism, which involves the elimination of unneces... more 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 model organism for studying the autophagic machinery per se, and uncover its multidimensional roles in the maintenance of cellular and organismal homeostasis. The current protocol describes the in vivo detection and biochemical analysis of the autophagic substrate SQST-1, as an indicator of autophagic flux in C. elegans.
Mitochondria preserve metabolic homeostasis and integrate stress signals, to trigger cytoprotecti... more 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 mitochondrial iron-sulfur cluster binding protein, implicated in the pathogenesis of Wolfram neurodegenerative syndrome type 2, modulates longevity in the nematode Caenorhabditis elegans by engaging autophagy and the mitochondrial intrinsic apoptosis pathway. The anti-apoptotic protein CED-9 is the downstream effector that mediates CISD-1-dependent effects on proteostasis, neuronal integrity and lifespan. Moreover, intracellular iron abundance is critical for CISD-1 function, since mild iron supplementation is sufficient to decelerate ageing and partly ameliorate the disturbed mitochondrial bioenergetics and proteostasis of CISD-1 deficient...
Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite ... more Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite its crucial role in vital biological processes, exceeded iron levels can be harmful for cellular and organismal homeostasis, due to iron’s involvement in the generation of toxic hydroxyl radicals. As such, maintaining balanced iron levels is highly required in order for the organisms to avoid iron toxicity and at the same time preserve iron-dependent processes. This is achieved by the tight coordination of intricate systemic, cellular and subcellular mechanisms for iron absorption, excretion, utilization and storage. Those mechanisms decline during ageing, as well as in multiple human pathologies, leading to iron overload or deprivation, and eventually to death. To gain insight into how perturbations in iron homeostasis lead to disease, it is of great importance to use efficient methods for iron detection in distinct biological samples. Towards this direction, several biochemical and biophysical methods have been developed for the determination of iron and iron-containing compounds.
Autophagy is a universal cellular homeostatic process, required for the clearance of dysfunctiona... more 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, autophagy can also contribute to promote different modes of cell death, either through highly regulated signalling events, or in a more uncontrolled inflammatory manner. Conversely, apoptotic or necroptotic factors have also been implicated in the regulation of autophagy, while specific factors regulate both processes. Here, we survey both earlier and recent findings, highlighting the intricate interaction of autophagic and cell death pathways. We, Furthermore, discuss paradigms, where this cross-talk is disrupted, in the context of disease.
One-carbon metabolism (OCM) is a network of biochemical reactions delivering one-carbon units to ... more 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 supports glutathione production and regulation of the cellular redox state. Dietary intake of micronutrients, such as folates and amino acids, directly contributes to OCM, thereby adapting the cellular metabolic state to environmental inputs. The contribution of OCM to cellular proliferation during development and in adult proliferative tissues is well established. Nevertheless, accumulating evidence reveals the pivotal role of OCM in cellular homeostasis of non-proliferative tissues and in coordination of signaling cascades that regulate energy homeostasis and longevity. In this review, we summarize the current knowledge on OCM and relate...
Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite ... more Iron is a versatile trace metal, indispensable for the survival of all living organisms. Despite its crucial role in vital biological processes, exceeded iron levels can be harmful for cellular and organismal homeostasis, due to iron’s involvement in the generation of toxic hydroxyl radicals. As such, maintaining balanced iron levels is highly required in order for the organisms to avoid iron toxicity and at the same time preserve iron-dependent processes. This is achieved by the tight coordination of intricate systemic, cellular and subcellular mechanisms for iron absorption, excretion, utilization and storage. Those mechanisms decline during ageing, as well as in multiple human pathologies, leading to iron overload or deprivation, and eventually to death. To gain insight into how perturbations in iron homeostasis lead to disease, it is of great importance to use efficient methods for iron detection in distinct biological samples. Towards this direction, several biochemical and bio...
Autophagy is a well-conserved self-degrading mechanism, which involves the elimination of unneces... more 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 model organism for studying the autophagic machinery per se, and uncover its multidimensional roles in the maintenance of cellular and organismal homeostasis. The current protocol describes the in vivo detection and biochemical analysis of the autophagic substrate SQST-1, as an indicator of autophagic flux in C. elegans.
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