Po is used as an honorific, usually for someone who is older that you. 

Ninyo is you but plural. Mo is you, only singular, referring to only one person that is.

However, when you say ano po ang ginagawa mo?, it seems a little awkward because you are using an honorific but you directly address the person you are talking to. In Tagalog, when we use po or when we address older people, we don't use singular pronouns like mo. You should use ninyo.

I don't know if I explained that well.