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New aging-related molecular pathway discovered

Nieuwe verouderingsgerelateerde moleculaire route ontdekthow-1 is required for maximum UPRmtactivation. †a) Fluorescence images of UPRmt– reporter (hsp-6p::GFP) activation in L4 nuo-6(qm200< /i>) animals on check and how-1 RNAi† Scale bar 200 m. (B) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L4 nuo-6(qm200) animals on control and how-1 RNAi normalized to hsp-6p::GFP in a wildtype background on control RNAi (n = 8 and 15, respectively, mean and SD shown, unpaired t-test). †C) Fluorescence images of UPRmt– reporter (hsp-6p::GFP) activation in L3/L4 wild-type and how- 1 null (how-1(-/-)) animals on checkcco-1 and spg -7 RNAi† Scale bar 200 m. (d) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 wild-type and how-1(-/-) animals on check and cco-1 RNAi (n = 8,12.6 and 13, respectively, mean and SD shown, plain two-way ANOVA with Tukey’s multiple comparison test). †E) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 wild-type and how-1(-/-) animals on check and spg-7 RNAi (n = 7.15.6 and 18, respectively, mean and SD shown, plain two-way ANOVA with Tukey’s multiple comparison test). †f) Fluorescence images of UPRmt– reporter (hsp-6p::GFP) activation in L3/L4 Nuo-6(QM200) animals with (how-1(+/+)) and without (how-1(-/-how-1 † Scale bar 200 m. (G) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 nuo-6(qm200) animals with (how-1(+/+)) and without (how-1(-/-how-1 normalized to hsp-6p::GFP in a wild-type background (n = 22 for each condition, mean and SD shown, unpaired t-test). Credit: eLife (2022). DOI: 10.7554/eLife.71634″ width=”800″ height=”529″/>

hoe-1 is required for maximum UPRmt activation. †A) Fluorescence images of UPRmt news reporter (hsp-6p::GFP) activation in L4 nuo-6(qm200) animals to check and how-1 RNAi† Scale bar 200 m. (B) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L4 nuo-6(qm200) animals under control and how-1 RNAi normalized to hsp-6p::GFP in a wildtype background on control RNAi (n = 8 and 15, respectively, mean and SD shown, unpaired t-test). †C) Fluorescence images of UPRmt news reporter (hsp-6p::GFP) activation in L3/L4 wild-type and hoe-1 zero (hoe-1(-/-)) animals to checkcco-1and spg-7 RNAi† Scale bar 200 m. (d) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 wild-type and hoe-1(-/-) animals to check and cco-1 RNAi (n = 8.12.6 and 13, respectively, mean and SD shown, plain two-way ANOVA with Tukey’s multiple comparison test). †E) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 wild-type and hoe-1(-/-) animals to check and spg-7 RNAi (n = 7.15.6 and 18, respectively, mean and SD shown, plain two-way ANOVA with Tukey’s multiple comparison test). †f) Fluorescence images of UPRmt news reporter (hsp-6p::GFP) activation in L3/L4 nuo-6(qm200) animals with (hoe-1 (+/+)) and without (hoe-1(-/-hoe-1† Scale bar 200 m. (G) Quantification of the Fluorescence Intensity of hsp-6p::GFP in individual L3/L4 nuo-6(qm200) animals with (hoe-1 (+/+)) and without (hoe-1(-/-hoe-1 normalized to hsp-6p::GFP in a wild-type background (n = 22 for each condition, mean and SD shown, unpaired t-test). Credit: eLife (2022). DOI: 10.7554/eLife.71634

A collaborative project between the labs of Maulik Patel, assistant professor of biological sciences, and Kris Burkewitz, assistant professor of cell and developmental biology, has identified a novel molecular pathway that plays a key role in the ability of cells to sense and respond to stressed stress. mitochondria. Defects in mitochondrial function are particularly relevant for aging and age-related diseases.

Led by Patel Lab student James Held, the work showcased the combined expertise of the Patel and Burkewitz labs — in genetics and in cell biology and imaging, respectively. “While most of the field focuses on protein damage, Held and Patel had a very innovative idea to investigate whether mitochondrial stress is activated at the RNA level,” Burkewitz said. “When they found another surprise — indications that some of the key events in this new pathway occurred outside the mitochondria — we seized the opportunity to help them visualize these processes at the scale of individual organelles.”

Together, the researchers’ labs discovered a novel RNA-based cellular pathway that modulates the predominant mechanism that maintains mitochondrial function under stress.

Mitochondria are responsible for producing most of the energy our cells need, and mitochondrial decay is directly linked to aging and aging-related diseases. Given the importance of mitochondria, cells have a way of sensing and responding when mitochondria are under stress, but how they do this is not fully understood.

“This work helps identify cell pathways that are often disrupted in disease and old age,” Held said. “These can be used to cure disease and slow the aging process.”

“This work opens new avenues for investigating how cells feel and respond to stressed mitochondria that we hope to address in the near term,” Patel said. “In the long term, we hope to identify drug targets that allow us to manipulate these mitochondrial stress-sensitive pathways to maintain mitochondrial quality in disease and in old age.”

The research was published in eLife


Discovering clues for the regulation of mitochondria production in aging cells


More information:
James P Held et al, A tRNA processing enzyme is a key regulator of the mitochondrial unfolded protein response, eLife (2022). DOI: 10.7554/eLife.71634

Provided by Vanderbilt University


Quote: New aging-related molecular pathway discovered (2022, June 23) retrieved June 23, 2022 from https://phys.org/news/2022-06-aging-related-molecular-pathway.html

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