Related Experiment Video

Updated: May 5, 2026

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates
14:32

Deacetylation Assays to Unravel the Interplay between Sirtuins SIRT2 and Specific Protein-substrates

Published on: February 27, 2016

7.8K

SirT3 regulates the mitochondrial unfolded protein response

Luena Papa1, Doris Germain

  • 1Mount Sinai School of Medicine, Tisch Cancer Institute, Division of Hematology/Oncology, New York, New York, USA.

Molecular and Cellular Biology
|December 11, 2013
PubMed

Insights

Mitochondrial deacetylase SirT3 orchestrates antioxidant and mitophagy pathways to manage cancer cell stress. SirT3

Area of Science:

  • Mitochondrial Biology
  • Cancer Cell Biology
  • Cellular Stress Response

Background:

  • Cancer cells exhibit elevated oxidative stress from reactive oxygen species (ROS), driving malignant transformation.
  • High ROS levels can cause irreversible protein damage, leading to mitochondrial stress and cell death.
  • Mechanisms to overcome mitochondrial stress, such as the unfolded protein response (UPR(mt)), are crucial.

Purpose of the Study:

  • To investigate the novel role of mitochondrial deacetylase SirT3 in the mitochondrial unfolded protein response (UPR(mt)).
  • To elucidate how SirT3 influences cellular adaptation to proteotoxic and mitochondrial stress in cancer.

Main Methods:

  • Investigated the function of SirT3 in cells undergoing proteotoxic stress.
  • Analyzed the interplay between SirT3, antioxidant machinery, and mitophagy.
  • Examined the impact of SirT3 inhibition on mitochondrial integrity and cell viability.

Main Results:

  • SirT3 orchestrates both antioxidant defenses and mitophagy pathways.
  • Inhibition of SirT3 impairs the mitochondrial network and leads to cell death under proteotoxic stress.
  • SirT3 appears to differentiate between moderately stressed and irreversibly damaged mitochondria.

Conclusions:

  • SirT3 plays a dual role, acting as a tumor suppressor during transformation and promoting adaptation in established tumors.
  • SirT3 is essential for cancer cell adaptation to proteotoxic and mitochondrial stress.
  • This study reveals a novel mechanism by which SirT3 maintains cancer cell survival under stress.

More Related Videos

Measurements of Physiological Stress Responses in C. Elegans10:36

Measurements of Physiological Stress Responses in C. Elegans

Published on: May 21, 2020

14.0K

Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
5.6K
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...
2.2K
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,...
8.8K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.4K
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
Protein Modifications in the RER01:26

Protein Modifications in the RER

Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
5.6K