Related Experiment Video

Updated: Mar 21, 2026

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry
11:39

Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry

Published on: July 21, 2017

32.5K

Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages

Jacinta P W Lee1, Andrew Foote1, Huapeng Fan1

  • 1a Lupus Research Group, Center for Inflammatory Diseases, School of Clinical Sciences at Monash Health, Faculty of Medicine, Nursing and Health Sciences, Monash University , Clayton , Victoria , Australia.

Autophagy
|May 11, 2016
PubMed

Insights

Autophagy regulates macrophage secretion of macrophage migration inhibitory factor (MIF). Loss of autophagy enhances MIF secretion, dependent on mitochondrial reactive oxygen species (ROS), impacting inflammatory diseases and cancer.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine implicated in inflammatory diseases and cancer progression.
  • Autophagy, a cellular degradation process, is known to influence the secretion of other inflammatory cytokines in macrophages.
  • The specific role of autophagy in regulating MIF secretion remains largely unexplored.

Purpose of the Study:

  • To investigate the role of autophagy in regulating the secretion of macrophage migration inhibitory factor (MIF) in monocytes and macrophages.
  • To determine the involvement of mitochondrial reactive oxygen species (ROS) in this regulatory process.
  • To explore the impact of different autophagy induction methods on MIF secretion.

Main Methods:

  • Pharmacological inhibition and siRNA silencing of Atg5 to impair autophagy.
  • Assessment of MIF secretion levels in monocytes and macrophages.
  • Evaluation of the role of mitochondrial ROS using specific inhibitors or inducers.
  • Manipulation of autophagy via MTOR inhibitors and amino acid starvation.

Main Results:

  • Loss of autophagy, induced by Atg5 inhibition, significantly enhanced MIF secretion in monocytes and macrophages.
  • This enhanced MIF secretion was dependent on mitochondrial ROS production.
  • Amino acid starvation, a method to induce autophagy, also increased MIF secretion, independently of Atg5 but dependent on mitochondrial ROS.
  • MTOR inhibitors, used to induce autophagy, did not affect MIF secretion.

Conclusions:

  • Autophagic regulation of mitochondrial ROS is a critical mechanism controlling inflammatory cytokine (MIF) secretion in macrophages.
  • These findings highlight a novel pathway with potential implications for understanding and treating inflammatory diseases and cancers.
  • Targeting autophagy and mitochondrial ROS may offer therapeutic strategies for MIF-related pathologies.
Keywords:
LPSautophagosomecytokinesinflammationmacrophagereactive oxygen speciesstarvation

More Related Videos

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy07:20

Exploring the Regulation of Lipid Droplet Catabolism through Lipophagy

Published on: January 31, 2025

1.4K
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging09:10

Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging

Published on: July 16, 2021

3.7K

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,...
6.1K
Autophagic Cell Death01:18

Autophagic Cell Death

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...
4.9K
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...
10.4K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

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...
5.0K
Phagocytosis of Apoptotic Cells01:17

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
Normal cells contain receptors that prevent them from being recognized...
5.5K
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
3.0K