Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of
            <i>C. elegans</i>

Calculli, Giuseppe; Lee, Hyun Ju; Shen, Koning; Pham, Uyen; Herholz, Marija; Trifunović, Aleksandra; Dillin, Andrew

doi:10.1126/sciadv.abg3012

Cited by 29 publications

(12 citation statements)

References 61 publications

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“…Increase in filamentous muscle mitochondria following 5day exercise protocol using the myo-3::gfp reporter strain and scored according to [41], scale bar = 50μm (a). Representative images of myo3-p::tomm20::Rosella mitophagy reporter following 5 day swimming protocol (b).…”

Section: Resultsmentioning

confidence: 99%

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Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Qin

Casas-Martinez

Zarzuela

et al. 2022

Preprint

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Exercise generates a site-specific increase in Reactive Oxygen Species (ROS) within muscle required for a beneficial adaptive response by activation of specific signalling pathways. Here, we demonstrate that Peroxiredoxin 2 (Prdx2), an abundant cytoplasmic 2-Cys peroxiredoxin, is required for the adaptive beneficial hormesis response to H2O2. A short bolus addition of H2O2 increases mitochondrial capacity and improves myogenesis of cultured myoblasts, this beneficial adaptive response was suppressed in myoblasts with decreased expression of cytoplasmic Prdxs. A swimming exercise protocol in C. elegans increased mitochondrial content, fitness, survival and longevity in wild type (N2) worms. In contrast, prdx-2 mutant worms had decreased fitness, disrupted mitochondria, reduced survival and lifespan following exercise. Global proteomics following exercise identified distinct changes in the proteome of N2 and prdx-2 mutants. Furthermore, a redox proteomic approach to quantify reversible oxidation of individual Cysteine residues revealed a relatively more oxidised redox state following exercise in the prdx-2 mutants. Our results demonstrate that conserved cytoplasmic 2-Cys Peroxiredoxins are required for the beneficial adaptive response to a physiological stress.

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Section: Resultsmentioning

confidence: 99%

“…Figure 5. Exercise protocol promotes mitochondrial dynamics, function and content but not in prdx-2 mutants.Increase in filamentous muscle mitochondria following 5day exercise protocol using the myo-3::gfp reporter strain and scored according to[41] , scale bar = 50µm (a). Representative images of myo3-p::tomm20::Rosella mitophagy reporter following 5 day…”

mentioning

confidence: 99%

Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Qin

Casas-Martinez

Zarzuela

et al. 2022

Preprint

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“…It has been shown that neuronal induction of UPR mt by the accumulation of expanded-polyQ aggregates leads to UPR mt induction in the intestine, and depends on the neuronal release of serotonin and long-range Wnt signaling pathway ( Berendzen et al, 2016 ; Q.; Zhang et al, 2018 ). In addition to the nervous system, other tissues can also communicate their proteostasis status and induce the UPR mt in distal tissues ( Calculli et al, 2021 ). For instance, aggregation of the germ granule component PGL-1 triggers intracellular changes in the mitochondrial network of C. elegans germline cells.…”

Section: Adaptive Stress Response Mechanismsmentioning

confidence: 99%

“…For instance, aggregation of the germ granule component PGL-1 triggers intracellular changes in the mitochondrial network of C. elegans germline cells. In turn, the germline releases long-range WNT ligands that induce an overactivation of the UPR mt in somatic tissues, promoting somatic mitochondrial fragmentation and aggregation of proteins linked with age-related neurodegenerative diseases such amyotrophic lateral sclerosis and Huntington’s ( Calculli et al, 2021 ).…”

Section: Adaptive Stress Response Mechanismsmentioning

confidence: 99%

Insights Into the Links Between Proteostasis and Aging From C. elegans

Zhang

Koyuncu

2022

Front. Aging

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Protein homeostasis (proteostasis) is maintained by a tightly regulated and interconnected network of biological pathways, preventing the accumulation and aggregation of damaged or misfolded proteins. Thus, the proteostasis network is essential to ensure organism longevity and health, while proteostasis failure contributes to the development of aging and age-related diseases that involve protein aggregation. The model organism Caenorhabditis elegans has proved invaluable for the study of proteostasis in the context of aging, longevity and disease, with a number of pivotal discoveries attributable to the use of this organism. In this review, we discuss prominent findings from C. elegans across the many key aspects of the proteostasis network, within the context of aging and disease. These studies collectively highlight numerous promising therapeutic targets, which may 1 day facilitate the development of interventions to delay aging and prevent age-associated diseases.

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“…Increased PGL-1 aggregation resulted in a significant decrease in mitochondrial protein levels in the germline, which resulted in a Wnt-dependent transmission of mitochondrial stress signals to the soma. Specifically, PGL-1 aggregation in the germline resulted in an EGL-20 (Wnt ligand) and MIG-1 (Wnt receptor)-dependent mitochondrial fragmentation and UPR MT induction in the soma ( Calculli et al, 2021 ). However, it is still unclear whether this somatic UPR MT induction is beneficial to organismal health and lifespan.…”

Section: Introductionmentioning

confidence: 99%

Hijacking Cellular Stress Responses to Promote Lifespan

2022

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Organisms are constantly exposed to stress both from the external environment and internally within the cell. To maintain cellular homeostasis under different environmental and physiological conditions, cell have adapted various stress response signaling pathways, such as the heat shock response (HSR), unfolded protein responses of the mitochondria (UPRMT), and the unfolded protein response of the endoplasmic reticulum (UPRER). As cells grow older, all cellular stress responses have been shown to deteriorate, which is a major cause for the physiological consequences of aging and the development of numerous age-associated diseases. In contrast, elevated stress responses are often associated with lifespan extension and amelioration of degenerative diseases in different model organisms, including C. elegans. Activating cellular stress response pathways could be considered as an effective intervention to alleviate the burden of aging by restoring function of essential damage-clearing machinery, including the ubiquitin-proteosome system, chaperones, and autophagy. Here, we provide an overview of newly emerging concepts of these stress response pathways in healthy aging and longevity with a focus on the model organism, C. elegans.

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Systemic regulation of mitochondria by germline proteostasis prevents protein aggregation in the soma of C. elegans

Cited by 29 publications

References 61 publications

Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Peroxiredoxin 2 is required for the redox mediated adaptation to exercise

Insights Into the Links Between Proteostasis and Aging From C. elegans

Hijacking Cellular Stress Responses to Promote Lifespan

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