Tissue Specific Distribution of Pyrimidine Deoxynucleoside Salvage Enzymes Shed Light on the Mechanism of Mitochondrial DNA Depletion

Sammanfattning

Deficiency in thymidine kinase 2 (TK2) activity due to genetic alterations caused tissue specific mitochondrial DNA (mtDNA) depletion syndrome with symptoms resembling these of AIDS patients treated with nucleoside analogues. Mechanisms behind this mitochondrial effects is still not well understood. With rat as a model we isolated mitochondrial and cytosolic fractions from major organs and studied enzymes involved in thymidine (dT) and deoxycytidine (dC) phosphorylation by using ionic exchange column chromatography. A cytosolic form of TK2 was identified in all tested tissues in addition to mitochondrial TK2. TK1 was detected in liver and spleen cytosolic extracts while dCK was found in liver, spleen and lung cytosolic extracts. Thus, the nature of dT and dC salvage enzymes in each tissue type was determined. In most tissues TK2 is the only salvage enzyme present except liver and spleen. These results may help to explain the mechanisms of mitochondrial toxicity of antiviral nucleoside analogues and mtDNA depletion caused by TK2 deficiency.

Nyckelord

Thymidine kinase 2; rat tissue; mitochondrial; cytosolic; mitochondrial DNA depletion

Publicerad i

Nucleosides, Nucleotides and Nucleic Acids
2010, volym: 29, nummer: 4-6, sidor: 400-403
Utgivare: TAYLOR & FRANCIS INC

SLU författare

• Wang, Liya

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

• Eriksson, Staffan

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Husdjursvetenskap
Veterinärmedicin

Publikationens identifierare

• DOI: https://doi.org/10.1080/15257771003741042

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/60591