Proposed model on the effect of cigarette smoke induced mitochondrial changes. Cigarette smoke is able to generate intracellular ROS production of which mitochondria are the main producers. ROS can damage important cellular components like nuclear DNA and organelles. Additionally, endogenous ROS affect mitochondrial DNA, membrane lipids and proteins, including fission/fusion proteins and PINK1, and induce oxidative modification or blocking of the OXPHOS system. Upon persistent mitochondrial damage or oxidative stress exceeding the anti-oxidant response, mitochondrial dysfunction will be introduced. Mitochondrial dysfunction and ROS from cigarette smoke may eventually induce inflammation, premature ageing and the onset of COPD.