Mitochondrial efficiency is increased in axenically cultured Caenorhabditis elegans

Castelein, Natascha; Muschol, Michael; Dhondt, Ineke; Cai, Huaihan; Vos, Winnok H. De; Dencher, Norbert A.; Braeckman, Bart P.

doi:10.1016/j.exger.2014.02.009

Cited by 17 publications

(21 citation statements)

References 62 publications

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“…The metabolic status of the microbes and their pathogenicity (Kim, 2013) to the host are both key determinates of host–microbe interactions that impact health and lifespan. Previous attempts to synthesize a defined chemical diet for C. elegans have been unsuccessful for lifespan studies (Houthoofd et al, 2002a; Johnson et al, 1984; Lenaerts et al, 2008; Castelein et al, 2014). Formulation of bacteria-free culture systems has always impacted developmental timing, growth, metabolism and reproduction (Houthoofd et al, 2002a; Johnson et al, 1984; Castelein et al, 2014; Szewczyk et al, 2006).…”

Section: The Future Requires a Defined Dietmentioning

confidence: 99%

Gene-diet interactions and aging in C. elegans

Yen

Curran

2016

Experimental Gerontology

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Diet is the most variable aspect of life history, as most individuals have a large diversity of food choices, varying in the type and amount that they ingest. In the short-term, diet can affect metabolism and energy levels. However, in the long run, the net deficiency or excess of calories from diet can influence the progression and severity of age-related diseases. An old and yet still debated question is: how do specific dietary choices impact health- and lifespan? It is clear that genetics can play a critical role — perhaps just as important as diet choices. For example, poor diet in combination with genetic susceptibility can lead to metabolic disorders, such as obesity and type 2 diabetes. Recent work in Caenorhabditis elegans has identified the existence of diet-gene pairs, where the consequence of mutating a specific gene is only realized on specific diets. Many core metabolic pathways are conserved from worm to human. Although only a handful of these diet-gene pairs has been characterized, there are potentially hundreds, if not thousands, of such interactions, which may explain the variability in the rates of aging in humans and the incidence and severity of age-related diseases.

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Section: The Future Requires a Defined Dietmentioning

confidence: 99%

Gene-diet interactions and aging in C. elegans

Yen

Curran

2016

Experimental Gerontology

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“…These observations suggest that DR may not cause mitochondrial proteotoxic stress and its beneficial effect on life span is independent of the UPR mt . On the other hand, we found enhanced mitochondrial performance ( 8 ) and increased stress resistance ( 3 ) in ADR worms, hinting at enhanced proteostasis. Therefore, we reasoned that unfolded protein responses and in particular the UPR mt may underlie the life span–doubling effect of ADR.…”

Section: Resultsmentioning

confidence: 72%

“…Probably, this mechanism is distinct from that of most other DR regimens, as was recently shown in a genetic screen ( 6 ). Our previous findings suggest that increased stress resistance and enhanced mitochondrial function may play a vital role in ADR-induced longevity ( 3 , 7 , 8 ). These observations lead us to investigate the role of the mitochondrial unfolded protein response (UPR mt ) and mitohormesis in ADR-mediated life-span extension.…”

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confidence: 99%

Life-Span Extension by Axenic Dietary Restriction Is Independent of the Mitochondrial Unfolded Protein Response and Mitohormesis in Caenorhabditis elegans

Cai

Rasulova

Vandemeulebroucke

et al. 2017

The Journals of Gerontology: Series A

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In Caenorhabditis elegans, a broad range of dietary restriction regimens extend life span to different degrees by separate or partially overlapping molecular pathways. One of these regimens, axenic dietary restriction, doubles the worm’s life span but currently, almost nothing is known about the underlying molecular mechanism. Previous studies suggest that mitochondrial stress responses such as the mitochondrial unfolded protein response (UPRmt) or mitohormesis may play a vital role in axenic dietary restriction–induced longevity. Here, we provide solid evidence that axenic dietary restriction treatment specifically induces an UPRmt response in C elegans but this induction is not required for axenic dietary restriction–mediated longevity. We also show that reactive oxygen species–mediated mitohormesis is not involved in this phenotype. Hence, changes in mitochondrial physiology and induction of a mitochondrial stress response are not necessarily causal to large increases in life span.

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“…In extensu, the workflow is easily amenable to the analysis of other organelles (e.g. the ER) and while the method was originally conceived for cell-based assays, it has already been adapted to cater for measurements of redox metabolism and mitochondrial morphology or density in C. elegans (Back et al 2012;Castelein et al 2014;de Boer et al 2015;. Despite proven performance in 2D, a challenge resides in the 3D nature of the imaged tissue, demanding confocal instead of widefield acquisition and more complex 3D segmentation procedures.…”

Section: Discussionmentioning

confidence: 99%

Integrated High-Content Quantification of Intracellular ROS Levels and Mitochondrial Morphofunction

Sieprath

Corne

Willems

et al. 2016

Advances in Anatomy, Embryology and Cell Biology

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Oxidative stress arises from an imbalance between the production of reactive oxygen species (ROS) and their removal by cellular antioxidant systems. Especially under pathological conditions, mitochondria constitute a relevant source of cellular ROS. These organelles harbor the electron transport chain, bringing electrons in close vicinity to molecular oxygen. Although a full understanding is still lacking, intracellular ROS generation and mitochondrial function are also linked to changes in mitochondrial morphology. To study the intricate relationships between the different factors that govern cellular redox balance in living cells, we have developed a high-content microscopy-based strategy for simultaneous quantification of intracellular ROS levels and mitochondrial morphofunction. Here, we summarize the principles of intracellular ROS generation and removal, and we explain the major considerations for performing quantitative microscopy analyses of ROS and mitochondrial morphofunction in living cells. Next, we describe our workflow and finally, we illustrate that a multiparametric readout enables the unambiguous classification of chemically perturbed cells as well as laminopathy patient cells. Principles of intracellular ROS generation and removalReactive oxygen species (ROS) are small, short-lived derivatives of molecular oxygen (O 2 ) of radical and non-radical nature (Halliwell and Gutteridge 2007 • ), nitrate radical (NO 3 • ) and many other nitrogen derivatives. ROS were originally described as molecular constituents of the defense system of phagocytic cells, but it has become clear that besides their damaging properties, they also function as signaling molecules and mediate a variety of other cellular responses including cell proliferation, differentiation, gene expression and migration (Lambeth 2004;Bartz and Piantadosi 2010). Intracellular ROS metabolismROS can be generated at various sites in the cell (Fig. 1A). This can be either deliberately, e.g. by NADPH oxidases (NOX), or as a byproduct, e.g. during normal cellular respiration in mitochondria (Babior 1999;Turrens 2003;Murphy 2009). The NOX family of NADPH oxidases (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) are proteins that transport electrons (e -) from NADPH across biological membranes (plasma or endomembranes) (Bedard and Krause 2007;Dupre-Crochet et al. 2013). The activation mechanisms and tissue distribution of the isoforms differ but they all use O 2 as e --acceptor, producing O 2•-. Through ROS generation, they play a role in many cellular processes including host defense, regulation of gene expression and cell differentiation (Bedard and Krause 2007). Despite their sometimes significant contribution to the global ROS pools, NOX are not the predominant source of intracellular ROS. Mitochondria are considered the major culprit, in particular under pathological conditions. Mitochondrial ROS are generated as a byproduct of the oxidative phosphorylation (OXPHOS, cf. below). Irrespective of its source, ROS production generally sta...

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Mitochondrial efficiency is increased in axenically cultured Caenorhabditis elegans

Cited by 17 publications

References 62 publications

Gene-diet interactions and aging in C. elegans

Gene-diet interactions and aging in C. elegans

Life-Span Extension by Axenic Dietary Restriction Is Independent of the Mitochondrial Unfolded Protein Response and Mitohormesis in Caenorhabditis elegans

Integrated High-Content Quantification of Intracellular ROS Levels and Mitochondrial Morphofunction

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