It matters what you wanna do , our trainer tells us that if were gonna do boxing only ( gloves ) , your thumb can be poiting downwards , this way though , you might hit your enemy with your fingers and not with your knuckles , or its more likely .
So if your doing some mma , your thumb should be pointing up , therefore you will be hitting enemy with the 2 main knuckles , but they will be the lowest ones when you look , if your dont turn your hand in the hook they will be the 2 upper knuckes ( index and middle finger knuckles are the ones Im talking about ) .