Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease

Renato X. Santos, Sónia C. Correia, Xiongwei Zhu, Mark A. Smith, Paula I. Moreira*, Rudy J. Castellani, Akihiko Nunomura, George Perry

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

133 Scopus citations


Significance: Mitochondria are fundamental to the life and proper functioning of cells. These organelles play a key role in energy production, in maintaining homeostatic levels of second messengers (e.g., reactive oxygen species and calcium), and in the coordination of apoptotic cell death. The role of mitochondria in aging and in pathophysiological processes is constantly being unraveled, and their involvement in neurodegenerative processes, such as Alzheimer's disease (AD), is very well known. Recent Advances: A considerable amount of evidence points to oxidative damage to mitochondrial DNA (mtDNA) as a determinant event that occurs during aging, which may cause or potentiate mitochondrial dysfunction favoring neurodegenerative events. Concomitantly to reactive oxygen species production, an inefficient mitochondrial base excision repair (BER) machinery has also been pointed to favor the accumulation of oxidized bases in mtDNA during aging and AD progression. Critical Issues: The accumulation of oxidized mtDNA bases during aging increases the risk of sporadic AD, an event that is much less relevant in the familial forms of the disease. This aspect is critical for the interpretation of data arising from tissue of AD patients and animal models of AD, as the major part of animal models rely on mutations in genes associated with familial forms of the disease. Future Directions: Further investigation is important to unveil the role of mtDNA and BER in aging brain and AD in order to design more effective preventive and therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)2444-2457
Number of pages14
JournalAntioxidants and Redox Signaling
Issue number18
StatePublished - Jun 20 2013

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Mitochondrial DNA oxidative damage and repair in aging and Alzheimer's disease'. Together they form a unique fingerprint.

Cite this