Related Experiment Video

Updated: Aug 7, 2025

Study of Protein-protein Interactions in Autophagy Research
14:08

Study of Protein-protein Interactions in Autophagy Research

Published on: September 9, 2017

9.2K

TNIP1 inhibits selective autophagy via bipartite interaction with LC3/GABARAP and TAX1BP1

François Le Guerroué1, Eric N Bunker1, William M Rosencrans2

  • 1Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.

Molecular Cell
|March 10, 2023
PubMed

Insights

TNIP1 acts as a brake on mitophagy, the process of clearing damaged mitochondria. Removing TNIP1 speeds up mitophagy, while adding it slows it down, revealing its role in regulating this crucial cellular cleanup.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Mitophagy is essential for cellular health, removing damaged mitochondria.
  • The precise regulation of mitophagy components remains incompletely understood.

Purpose of the Study:

  • To investigate the role of TNIP1 in regulating mitophagy.
  • To elucidate the molecular mechanisms by which TNIP1 controls mitophagy rates.

Main Methods:

  • Utilized TNIP1 knockout and ectopic expression in HeLa cells.
  • Investigated protein interactions using LIR motif and AHD3 domain analyses.
  • Examined the role of phosphorylation in TNIP1-FIP200 association.

Main Results:

  • TNIP1 knockout accelerated mitophagy; ectopic TNIP1 inhibited mitophagy.
  • TNIP1's LIR motif binds LC3/GABARAP proteins; AHD3 domain binds TAX1BP1.
  • Phosphorylation regulates TNIP1 interaction with FIP200, enabling competition with autophagy receptors.

Conclusions:

  • TNIP1 is identified as a negative regulator of mitophagy.
  • TNIP1 inhibits mitophagy by interfering with early autophagosome biogenesis.
  • TNIP1's function is mediated by its LIR motif, AHD3 domain, and phosphorylation-dependent interactions.
Keywords:
FIP200FIRLIRSelective autophagyTAX1BP1TBK1TNIP1mitophagymitophagy regulation

More Related Videos

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells09:10

siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells

Published on: October 28, 2019

7.3K
Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles06:58

Evaluation of LC3-II Release via Extracellular Vesicles in Relation to the Accumulation of Intracellular LC3-positive Vesicles

Published on: October 18, 2024

749

Related Concept Videos

Autophagy01:27

Autophagy

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,...
4.4K
Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.6K
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
9.1K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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...
3.8K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.5K
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.7K