Related Experiment Video
Updated: Oct 2, 2025
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
9.3K
Basal Autophagy Is Necessary for A Pharmacologic PPARα Transactivation
Eun Young Kim1, Jae Man Lee1,2
1Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
Cells
|February 25, 2022
Summary
Basal autophagy is essential for activating peroxisome proliferator-activated receptor alpha (PPARα). Autophagy defects prevent PPARα activation by blocking nuclear factor erythroid 2-related factor 2 (NRF2) translocation, impacting metabolic homeostasis.
Area of Science:
- Cellular Biology
- Metabolism
- Molecular Biology
Background:
- Autophagy is a vital catabolic process for nutrient recycling and energy homeostasis.
- Defects in autophagy are linked to various diseases, including cancer and neurodegeneration.
- Peroxisome proliferator-activated receptor alpha (PPARα) regulates fasting-associated metabolism.
Purpose of the Study:
- To investigate the relationship between autophagy and PPARα transactivation.
- To determine the role of NRF2 in mediating the effects of autophagy defects on PPARα.
- To explore the clinical implications of basal autophagy for PPARα ligand efficacy.
Main Methods:
- Utilized liver-specific Atg7 gene ablation in mice.
- Assessed the expression of PPARα target genes.
- Examined the impact of NRF2 activation on PPARα transactivation.
Main Results:
- Autophagy deficiency impaired PPARα target gene expression.
- NRF2 activation was sufficient to inhibit PPARα transactivation, dependent on the Nrf2 gene.
- Autophagy defects led to p62/SQSTM1 accumulation and NRF2 activation.
Conclusions:
- Basal autophagy is required for PPARα transactivation by preventing NRF2 nuclear translocation.
- This finding highlights the clinical significance of autophagy for the efficacy of synthetic PPARα ligands.
Related Concept Videos
01:27Autophagy
4.7K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.7K
01:25cAMP-dependent Protein Kinase Pathways
6.8K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.8K
01:18Autophagic Cell Death
3.6K
Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
3.6K
01:36Delivery Pathways to the Lysosome
8.0K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
8.0K
01:22PI3K/mTOR/AKT Signaling Pathway
4.1K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
4.1K
03:03mTOR Signaling and Cancer Progression
3.9K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.9K