Related Experiment Video

Updated: Apr 18, 2026

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy
09:29

Time-Lapse Video Microscopy for Assessment of EYFP-Parkin Aggregation as a Marker for Cellular Mitophagy

Published on: May 4, 2016

7.7K

The mitochondrial protein BNIP3L is the substrate of PARK2 and mediates mitophagy in PINK1/PARK2 pathway

Feng Gao1, Dong Chen2, Jianmin Si1

  • 1Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 215021, China, Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, Anhui 230027, China and.

Human Molecular Genetics
|January 24, 2015
PubMed

Insights

Parkinson's disease involves mitochondrial dysfunction. BNIP3L protein, downstream of PINK1/PARK2, drives mitophagy by targeting damaged mitochondria for degradation, crucial for neuronal survival.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Genetics

Background:

  • Mitochondrial dysfunction is a key factor in Parkinson's disease (PD) pathogenesis.
  • Maintaining dopaminergic (DA) neuronal survival relies on clearing damaged mitochondria via quality control systems.
  • BNIP3L/Nix, a mitochondrial outer membrane protein, is essential for selective mitochondrial clearance.

Purpose of the Study:

  • To investigate the role of BNIP3L in the PINK1/PARK2 pathway in Parkinson's disease.
  • To elucidate the mechanism by which BNIP3L induces mitophagy.
  • To determine the dependency of BNIP3L-mediated mitophagy on PARK2.

Main Methods:

  • Investigated BNIP3L's function downstream of the PINK1/PARK2 pathway.
  • Examined BNIP3L ubiquitination by PARK2 and subsequent NBR1 recruitment.
  • Utilized Drosophila models (pink1 and park mutants) and cellular models with mitochondrial complex I inhibitors (rotenone, 6-OHDA, MPP+).

Main Results:

  • BNIP3L acts downstream of PINK1/PARK2 to induce mitophagy.
  • PARK2 ubiquitinates BNIP3L, recruiting NBR1 to target mitochondria for degradation.
  • BNIP3L rescues mitochondrial defects in pink1 mutant Drosophila but not park mutant Drosophila.
  • Improper BNIP3L degradation impairs mitophagy in cells treated with mitochondrial toxins.

Conclusions:

  • BNIP3L is a substrate of PARK2, promoting mitophagy within the PINK1/PARK2 pathway relevant to PD.
  • PARK2 is essential for BNIP3L-mediated clearance of damaged mitochondria.
  • Dysregulation of BNIP3L degradation contributes to mitochondrial defects in PD pathogenesis.

More Related Videos

Author Spotlight: Fluorescence-Based Quantification of Mitochondrial Membrane Potential and Superoxide Levels Using Live Imaging in HeLa Cells06:57

Author Spotlight: Fluorescence-Based Quantification of Mitochondrial Membrane Potential and Superoxide Levels Using Live Imaging in HeLa Cells

Published on: May 12, 2023

9.5K
Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy07:40

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy

Published on: May 26, 2023

1.8K

Related Concept Videos

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...
11.8K
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
13.8K
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...
9.3K
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...
6.5K
piRNA - Piwi-interacting RNAs02:57

piRNA - Piwi-interacting RNAs

PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.9K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
16.2K