Comprehensive ubiquitome analysis reveals persistent mitochondrial remodeling disruptions from doxorubicin-induced cardiotoxicity in aged CD-1 male mice
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
View abstract on PubMed
Summary
This summary is machine-generated.Doxorubicin (DOX) causes lasting heart damage in aged mice, impairing mitochondrial function and increasing protein ubiquitination. These molecular changes persist for months after treatment, highlighting the need for extended patient monitoring.
Area Of Science
- Biochemistry
- Cardiology
- Molecular Biology
Background
- Doxorubicin (DOX) cardiotoxicity has long-term effects, with mechanisms poorly understood.
- Aging exacerbates DOX-induced heart damage.
Purpose Of The Study
- To investigate the enduring cardiac molecular impacts of DOX in aged mice.
- Focus on ubiquitinated proteins and mitochondrial function.
Main Methods
- Aged male CD-1 mice received DOX or saline.
- Cardiac tissue analyzed 2 months post-administration.
- Assessed protein ubiquitination, E3 ligase levels, mitochondrial markers, and autophagy-related proteins.
Main Results
- DOX induced cardiac structural changes and increased proteolytic activity.
- Elevated protein ubiquitination observed, despite decreased Atrogin-1.
- Increased poly-ubiquitination of sarcomere and mitochondrial proteins.
- Enhanced mitochondrial density and citrate synthase activity.
- Reduced mitochondrial biogenesis and autophagy markers (PGC-1α, Beclin1, LC3).
Conclusions
- DOX causes persistent mitochondrial dysfunction and accumulation of damaged mitochondria in aged hearts.
- Impaired protein ubiquitination and disrupted mitochondrial remodeling are lasting consequences of DOX treatment.
- Findings support extended clinical surveillance for DOX-treated patients due to enduring cardiotoxicity.
Contact us if these videos are not relevant.
Contact us if these videos are not relevant.
Related Concept Videos
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...