**5.3. Mitochondrial alterations**

Another proposed mechanism for HAART-associated dyslipidemia is the mitochondrial alterations induced by HAART, especially with PI-based therapy. The hypothesis is that the HAART regimens will cause mitochondrial disturbances by inhibiting the mitochondrial DNA (mtDNA)-polymerase γ, leading to mitochondrial DNA depletion, respiratory chain dysfunc‐ tion and reduced energy production by cells [62, 63]. This disturbance in the mitochondrial respiratory chain may promote metabolic disorders in adipocytes, promote lipodystrophy syndrome and increase plasma lipid levels. Moreover, interference between PIs and cellular protease could also trigger the development of metabolic alterations because some proteases are essential for mitochondrial biogenesis and metabolic function. Furthermore, functional changes of mitochondria in skeletal tissue promote insulin resistance and consequent dysli‐ pidemia [62-64].
