Figure 1.

To form microtubules, α- and β-tubulin molecules join to form a heterodimer. These dimers then attach to other dimers forming oligomers that elongate into protofilaments; eventually, the oligomers will join to give rise to a ringed microtubule. Microtubules or unpolymerized tubulin bind microtubule-associated proteins (MAPs), which regulate polymerization, facilitate assembly, stabilize the microtubules and regulate microtubular transport of macromolecules and vesicles. The HIV-1 Tat protein binds to αβ-tubulin dimers and microtubules thus enhancing microtubule polymerization, and to the microtubule-associated protein LIS1, which is also known to facilitate assembly of microtubules. Disturbance of the dynamics of microtubular network formation activates the intrinsic mitochondrial apoptotic pathway. Pro-apoptotic Bcl2 family members – in particular, Bim – are recruited to the mitochondrion; as a consequence, the mitochondrial membrane potential collapses, and pro-apoptotic factors are released into the cytoplasm. These include reactive oxygen intermediates (ROIs), apoptosis-inducing factor (AIF), and cytochrome c, among others. Release of cytochrome c is a point of no return as it leads to autoactivation of caspase 9, which in turn proceeds to cleave the downstream effector caspases (caspase 3, 6, etc.).