Depart from South American capital, short of oxygen (4)
I believe the answer is:
quit
'depart from' is the definition.
(thesaurus)
'south american capital short of oxygen' is the wordplay.
'south american capital' becomes 'quito' (capital of Ecuador).
'short of' suggests deleting specific letters.
'oxygen' becomes 'o' (atomic symbol for oxygen).
'quito' with 'o' taken away is 'QUIT'.
(Other definitions for quit that I've seen before include "Leave (one's job)" , "Pay off (a debt)" , "Discontinue an activity" , "Give up (smoking?)" , "Leave office" .)