The texture regions inside don't need to be powers of two.
But texture compression cells are often 4x4 so you have to be careful when using compressed textures that the edges of two texture regions don't share the same cell or they'll be compressed together which will degrade the quality if they have different colors.
You should leave a N pixel border around your regions where you extend the colors outward. Where N is 4 for compressed textures and a multiple of that if you're going to be using mipmaps.
So the compression, interpolation and mipmap don't draw using neighbor texels that are the wrong color at the seams.