Rheb and mammalian target of rapamycin in mitochondrial homoeostasis
Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermedia...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2013-01-01
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| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130185 |
| _version_ | 1819028463044001792 |
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| author | Marlous J. Groenewoud Fried J. T. Zwartkruis |
| author_facet | Marlous J. Groenewoud Fried J. T. Zwartkruis |
| author_sort | Marlous J. Groenewoud |
| collection | DOAJ |
| description | Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria. In the cytoplasm, the protein complex mTORC1 couples growth-promoting signals with anabolic processes, in which mitochondria play an essential role. Here, we review the involvement of mTORC1 and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of mTORC1 affect the glycolytic flux and the rate of mitophagy, and include regulation of the transcription factors HIF1α and YY1/PGC-1α. We also discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen species signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1. |
| first_indexed | 2024-12-21T05:58:45Z |
| format | Article |
| id | doaj.art-ad07515f7c7246b685cf512a1234a562 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-12-21T05:58:45Z |
| publishDate | 2013-01-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-ad07515f7c7246b685cf512a1234a5622022-12-21T19:13:48ZengThe Royal SocietyOpen Biology2046-24412013-01-0131210.1098/rsob.130185130185Rheb and mammalian target of rapamycin in mitochondrial homoeostasisMarlous J. GroenewoudFried J. T. ZwartkruisMitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria. In the cytoplasm, the protein complex mTORC1 couples growth-promoting signals with anabolic processes, in which mitochondria play an essential role. Here, we review the involvement of mTORC1 and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of mTORC1 affect the glycolytic flux and the rate of mitophagy, and include regulation of the transcription factors HIF1α and YY1/PGC-1α. We also discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen species signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1.https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130185mammalian target of rapamycinmitochondriametabolismrhebmitophagy |
| spellingShingle | Marlous J. Groenewoud Fried J. T. Zwartkruis Rheb and mammalian target of rapamycin in mitochondrial homoeostasis Open Biology mammalian target of rapamycin mitochondria metabolism rheb mitophagy |
| title | Rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| title_full | Rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| title_fullStr | Rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| title_full_unstemmed | Rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| title_short | Rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| title_sort | rheb and mammalian target of rapamycin in mitochondrial homoeostasis |
| topic | mammalian target of rapamycin mitochondria metabolism rheb mitophagy |
| url | https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.130185 |
| work_keys_str_mv | AT marlousjgroenewoud rhebandmammaliantargetofrapamycininmitochondrialhomoeostasis AT friedjtzwartkruis rhebandmammaliantargetofrapamycininmitochondrialhomoeostasis |