**6. Conclusions**

Cholesterol is a very important lipid that controls several cellular processes. This chapter describes how cholesterol is organized in cellular membranes and how it regulates and orchestrates the contractile machinery in muscle and nonmuscle cells. Cholesterol and RhoA protein prenylation share the same synthetic route: the mevalonate pathway. By lowering cholesterol concentration, using either chelating agents, such as MβCD, or inhibitors of HMG-CoA reductase, such as statins, one can observe opposite effects on actin cytoskeleton organization and contractile behavior. Cellular treatments with statins lead to a less-contractile profile, since this drug depletes the amount of prenylated RhoA, which, in turn, is the main upstream regulator of contractility in nonmuscle cells. On the other hand, MβCD-mediated cholesterol depletion induces RhoA activation, stress fiber formation, and increase in cortical stiffness pointing toward a more contractile behavior. In muscle cells, the results are even more intriguing: treatments with either statins or MβCD lead to myofibril disorganization, increase of contraction rate and defects in cell relaxation and in the ability of cells to handle intracellular Ca2+. The reason why muscle and nonmuscle cells behave differently regarding cholesterol depletion is not completely understood and further investigation needs to be performed in order to elucidate this paradigm.

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