Related Experiment Video

Updated: Aug 18, 2025

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

7.2K

Mitolysosome exocytosis: a novel mitochondrial quality control pathway linked with parkinsonism-like symptoms

Feixiang Bao1,2, Lingyan Zhou1,2,3, Jiahui Xiao1,2,3

  • 1CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences; Guangzhou Medical University, Guangzhou, China.

Biochemical Society Transactions
|December 9, 2022
PubMed

Insights

Researchers discovered a new way cells clear damaged mitochondria using mitolysosome exocytosis, a process not involving autophagosomes. This pathway, triggered by flunarizine, may explain how this drug causes parkinsonism.

Area of Science:

  • Cellular Biology
  • Mitochondrial Dynamics
  • Neurodegenerative Diseases

Background:

  • Mitochondrial quality control is vital for cellular health and function.
  • While mitophagy and mitochondrial-derived vesicles are known pathways, the complete mechanisms remain unclear.
  • Flunarizine (FNZ) is known to induce parkinsonism.

Purpose of the Study:

  • To investigate novel mechanisms of mitochondrial quality control beyond canonical pathways.
  • To elucidate the role of mitolysosome exocytosis in cellular mitochondrial clearance.
  • To explore the potential link between FNZ-induced mitochondrial clearance and parkinsonism.

Main Methods:

  • Investigated flunarizine (FNZ)-induced mitochondrial clearance in cellular models.
  • Utilized advanced microscopy and biochemical assays to track mitochondrial fate.
  • Examined the involvement of lysosomes and autophagosomes in the clearance process.

Main Results:

  • Discovered a novel mitochondrial quality control pathway: mitolysosome exocytosis.
  • Demonstrated that this pathway directly engulfs mitochondria into lysosomes for secretion, independent of autophagosomes.
  • Observed excessive mitolysosome exocytosis in FNZ-treated cells.

Conclusions:

  • Mitolysosome exocytosis is a distinct and important mechanism for mitochondrial quality control.
  • Excessive mitolysosome exocytosis induced by FNZ is proposed as a cause of FNZ-induced parkinsonism.
  • This finding opens new avenues for understanding and potentially treating mitochondrial dysfunction in neurodegenerative diseases.
Keywords:
extracellular vesicleslysosomemitochondria-freemitochondrial quality controlparkinsonism

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

8.1K
Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease06:07

Author Spotlight: Establishing a New Fluorescence-Based Protocol for In Vivo Mitochondrial Morphology Analysis in Parkinson's Disease

Published on: June 23, 2023

1.7K

Related Concept Videos

Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
3.9K
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,...
3.2K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
995
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

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...
6.7K
Mitochondrial Protein Sorting01:39

Mitochondrial Protein Sorting

Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
4.4K
Mitochondrial Membranes01:45

Mitochondrial Membranes

A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
11.8K