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Updated: Nov 7, 2025

In Vitro Characterization of Histone Chaperones using Analytical, Pull-Down and Chaperoning Assays
Published on: December 29, 2021
Mitochondrial cytochrome c shot towards histone chaperone condensates in the nucleus
Katiuska González-Arzola1, Alejandra Guerra-Castellano1, Francisco Rivero-Rodríguez1
1Institute for Chemical Research (IIQ), Scientific Research Centre Isla de la Cartuja (cicCartuja), University of Seville - CSIC, Spain.
Abstract:
Despite mitochondria being key for the control of cell homeostasis and fate, their role in DNA damage response is usually just regarded as an apoptotic trigger. However, growing evidence points to mitochondrial factors modulating nuclear functions. Remarkably, after DNA damage, cytochrome c (Cc) interacts in the cell nucleus with a variety of well-known histone chaperones, whose activity is competitively inhibited by the haem protein. As nuclear Cc inhibits the nucleosome assembly/disassembly activity of histone chaperones, it might indeed affect chromatin dynamics and histone deposition on DNA. Several histone chaperones actually interact with Cc Lys residues through their acidic regions, which are also involved in heterotypic interactions leading to liquid-liquid phase transitions responsible for the assembly of nuclear condensates, including heterochromatin. This relies on dynamic histone-DNA interactions that can be modulated by acetylation of specific histone Lys residues. Thus, Cc may have a major regulatory role in DNA repair by fine-tuning nucleosome assembly activity and likely nuclear condensate formation.
Insights
Mitochondria
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Mitochondria are crucial for cell homeostasis and fate.
- Their role in DNA damage response is often limited to apoptosis.
- Emerging evidence suggests mitochondrial factors influence nuclear functions.
Purpose of the Study:
- To investigate the role of mitochondrial factors, specifically cytochrome c, in nuclear DNA damage response.
- To explore how cytochrome c modulates chromatin dynamics and nuclear condensate formation.
Main Methods:
- Investigated the interaction of nuclear cytochrome c with histone chaperones post-DNA damage.
- Analyzed the effect of cytochrome c on nucleosome assembly/disassembly activity.
- Examined histone chaperone interactions with cytochrome c's Lys residues and their role in phase transitions.
Main Results:
- Cytochrome c (Cc) interacts with nuclear histone chaperones after DNA damage.
- Nuclear Cc competitively inhibits histone chaperone activity, affecting nucleosome assembly.
- Cc may influence heterochromatin formation via histone chaperone interactions and phase transitions.
Conclusions:
- Cytochrome c plays a regulatory role in DNA repair beyond apoptosis.
- Nuclear Cc fine-tunes nucleosome assembly and nuclear condensate formation.
- Mitochondrial factors can significantly impact nuclear DNA repair mechanisms.
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