How should i sort “Last Update” Custom Column?

orderby will not contain the title of the column that is being clicked on, but its ID. Change your pre_get_posts filter to

function my_organization_orderby( $query ) {
    if( ! is_admin() )
        return;

    $orderby = $query->get( 'orderby');

    if( 'profile_updated_on' == $orderby ) {
        $query->set('meta_key','profile_updated_on');
        $query->set('orderby','meta_value_num');
    }
}