Parkinson’s disease (PD) is the second most common neurodegenerative disease, with patient numbers being expected to double worldwide in the next 20 years. The detailed molecular and cellular mechanisms underlying its pathogenesis remains unclear, although recent evidence has pointed towards the role of mitochondrial dysfunction in the onset of the disease. Mitochondria—small cellular ‘subunits’ involved in cell metabolism and energy generation—constantly and dynamically interact with each other, forming perpetually changing networks known as mitochondria interaction networks (MINs). The researchers therefore sought to understand the correlation between the mitochondrial impairments observed in PD and any specific network topological changes in MINs, with the aim of advancing the early diagnosis and classification of PD patients.
“Since conventional analysis focusing on individual mitochondria has not provided satisfying insights into PD pathogenesis, our pioneering work has gone a step forward by investigating the interaction networks between these organelles”, explains Dr. Feng He, Group Leader of the Immune Systems Biology Group of the LIH Department of Infection and Immunity and corresponding author of the publication.
Leveraging their strong expertise in network analysis and machine learning, the scientists analyzed a large 700 Gigabyte dataset of three-dimensional mitochondrial images of colonic neurons, collected from PD patients and healthy controls, and dopaminergic neurons, derived from stem cells. They found that particular network structure features within MINs were altered in PD patients compared to controls. For instance, in PD patients, mitochondria formed connected subnetworks that were generally larger than in healthy individuals. In line with this result, the efficiency of the energy and information transmission and distribution among the different mitochondria in PD patient MINs was significantly lower than in controls, suggesting that the longer ‘transmission delays’ were associated with the larger diameter of the components of the MINs observed