AI Article Synopsis

  • Myelodysplastic syndromes (MDS) are blood disorders leading to ineffective blood cell production and increased cell death, resulting in low blood cell counts.
  • Mitochondria, which manage cell energy and can accumulate iron, were studied to understand their role in the altered energy metabolism found in MDS and how factors like iron overload affect this process.
  • Findings indicated that MDS patients showed reduced energy production efficiency and higher oxidative stress, but iron chelation treatment improved some biochemical abnormalities in their cells, whereas similar treatments had lesser effects on healthy individuals.

Article Abstract

Myelodysplastic syndromes (MDS) are hematological malignancies characterized by ineffective hematopoiesis and increased apoptosis in the bone marrow, which cause peripheral cytopenia. Mitochondria are key regulators of apoptosis and a site of iron accumulation that favors reactive oxygen species (ROS) production with detrimental effects on cell survival. Although the energy metabolism could represent an attractive therapeutic target, it was poorly investigated in MDS. The purpose of the study was to analyze how the presence of myelodysplastic hematopoiesis, iron overload and chelation impact on mitochondrial metabolism. We compared energy balance, OxPhos activity and efficiency, lactic dehydrogenase activity and lipid peroxidation in mononuclear cells (MNCs), isolated from 38 MDS patients and 79 healthy controls. Our data show that ATP/AMP ratio is reduced during aging and even more in MDS due to a decreased OxPhos activity associated with an increment of lipid peroxidation. Moreover, the lactate fermentation enhancement was observed in MDS and elderly subjects, probably as an attempt to restore the energy balance. The biochemical alterations of MNCs from MDS patients have been partially restored by the in vitro iron chelation, while only slight effects were observed in the age-matched control samples. By contrast, the addition of iron chelators on MNCs from young healthy subjects determined a decrement in the OxPhos efficiency and an increment of lactate fermentation and lipid peroxidation. In summary, MDS-MNCs display an altered energy metabolism associated with increased oxidative stress, due to iron accumulation. This condition could be partially restored by iron chelation.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280296PMC
http://dx.doi.org/10.1038/s41598-020-66162-yDOI Listing

Publication Analysis

Top Keywords

energy metabolism
12
lipid peroxidation
12
iron overload
8
myelodysplastic syndromes
8
iron accumulation
8
energy balance
8
oxphos activity
8
mds patients
8
lactate fermentation
8
partially restored
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!