Lysosomal biogenesis
TFEB-driven expansion of the lysosomal compartment.
Making more recycling plants. Making more recycling plants.
The return arm of the lysosome-to-nucleus circuit (SET2012): mTORC1 phosphorylation keeps TFEB out of the nucleus, and when it is released TFEB expands the very organelle on which mTORC1 is regulated. This closes a genuine homeostatic loop that a linear diagram cannot show.
TL;DR. Lysosomal biogenesis appears in 3 curated studies in Oliver's mTOR Atlas: 3 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| Lysosomal biogenesis activates Lysosome mechanism: functional-consequence · this link in full · on the map table | More, fresher lysosomes change the very platform that controls mTORC1 – closing a loop back to where the signal started. A larger, renewed lysosomal compartment changes the platform on which mTORC1 is regulated – the return leg of the lysosome-to-nucleus circuit. A larger, renewed lysosomal compartment changes the platform on which mTORC1 is regulated – the return leg of the lysosome-to-nucleus circuit. Holds under: SET2012 establishes lysosome-to-nucleus signalling via mTOR and TFEB; the quantitative effect of compartment size on mTORC1 output is not resolved. plausible in people, not shown directly · emerging, few independent studies | M | SET2012, SET2011 |
| TFEB activates Lysosomal biogenesis mechanism: transcriptional · this link in full · on the map table | In the nucleus, TFEB switches on a whole gene package for cleanup and for building new lysosomes. Nuclear TFEB switches on the lysosomal and autophagy gene programme as a single coordinated module, expanding the lysosomal compartment. Nuclear TFEB switches on the lysosomal and autophagy gene programme as a single coordinated module, expanding the lysosomal compartment. Holds under: Transcriptional output measured as gene expression and lysosomal markers; how much the compartment actually expands varies with cell type and starvation depth. plausible in people, not shown directly · settled in the literature | M | SET2011, ROC2012 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 3 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2012 | M | The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis ROC2012 mTORC1 phosphorylates TFEB to control lysosomal and autophagy gene transcription. |
| 2012 | M | A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB SET2012 A lysosome-to-nucleus mechanism uses mTOR-dependent TFEB phosphorylation to sense lysosomal state. |
| 2011 | M | TFEB links autophagy to lysosomal biogenesis SET2011 Showed that TFEB drives a coordinated autophagy and lysosomal gene programme during starvation. In this paper TFEB was regulated by ERK2 phosphorylation; its control by mTORC1 at the lysosome was established in later work (SET2012). |
Related entities
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