Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.
Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol....
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-05-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1011700 |
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| author | Jeson J Li Nan Xin Chunxia Yang Bo G Kim Larissa A Tavizon Ruth Hong Jina Park Travis I Moore Rebecca George Tharyan Adam Antebi Hyun-Eui Kim |
| author_facet | Jeson J Li Nan Xin Chunxia Yang Bo G Kim Larissa A Tavizon Ruth Hong Jina Park Travis I Moore Rebecca George Tharyan Adam Antebi Hyun-Eui Kim |
| author_sort | Jeson J Li |
| collection | DOAJ |
| description | Maintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and improving the ER's ability to handle proteostasis. MERSR activation in both polyglutamine and amyloid-beta peptide-expressing C. elegans disease models also led to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling. |
| format | Article |
| id | doaj-art-e02446e1edcc4b0eb04cb0e8a3fa4420 |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-e02446e1edcc4b0eb04cb0e8a3fa44202025-08-20T01:52:54ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042025-05-01215e101170010.1371/journal.pgen.1011700Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis.Jeson J LiNan XinChunxia YangBo G KimLarissa A TavizonRuth HongJina ParkTravis I MooreRebecca George TharyanAdam AntebiHyun-Eui KimMaintaining protein homeostasis is essential for cellular health. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response, activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPRER), suggesting the presence of a Mitochondria to ER Stress Response (MERSR). During MERSR, the IRE1 branch of UPRER is inhibited, introducing a previously unknown regulatory component of MCSR. Moreover, proteostasis is enhanced through the upregulation of the PERK-eIF2α signaling pathway, increasing phosphorylation of eIF2α and improving the ER's ability to handle proteostasis. MERSR activation in both polyglutamine and amyloid-beta peptide-expressing C. elegans disease models also led to improvement in both aggregate burden and overall disease outcome. These findings shed light on the coordination between the mitochondria and the ER in maintaining cellular proteostasis and provide further evidence for the importance of intercompartmental signaling.https://doi.org/10.1371/journal.pgen.1011700 |
| spellingShingle | Jeson J Li Nan Xin Chunxia Yang Bo G Kim Larissa A Tavizon Ruth Hong Jina Park Travis I Moore Rebecca George Tharyan Adam Antebi Hyun-Eui Kim Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. PLoS Genetics |
| title | Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. |
| title_full | Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. |
| title_fullStr | Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. |
| title_full_unstemmed | Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. |
| title_short | Unveiling the intercompartmental signaling axis: Mitochondrial to ER Stress Response (MERSR) and its impact on proteostasis. |
| title_sort | unveiling the intercompartmental signaling axis mitochondrial to er stress response mersr and its impact on proteostasis |
| url | https://doi.org/10.1371/journal.pgen.1011700 |
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