Figure. (Top left) Research aim. (Top right) Schema of mitochondrial respiratory chain supercomplex localization and function. (Bottom left) Analysis of supercomplex formation by hrCN-PAGE and in-gel activity assay. (Bottom right) Conclusion: “Large” supercomplex formation decrease correlated with the progression of neurodegenerative diseases.
Summary of the Announcement:
Neurodegenerative diseases are assumably caused, in part, by mitochondrial dysfunction in the central nervous system. However, tracking the corresponding dynamics has been difficult. A research group led by Associate Professor Ayako Okado-Matsumoto from the Department of Biology at Toho University and Professor Ryuji Sakakibara (at the time of the study) from the Department of Neurology at Toho University Medical Center Sakura Hospital focused on the mitochondria in peripheral blood leukocytes, which could be less invasively analyzed, and discovered that changes in respiratory chain supercomplex formation correlate with disease progression.
The researchers analyzed respiratory chain supercomplex formation using high-resolution Clear Native-Polyacrylamide Gel Electrophoresis (hrCN-PAGE), enabling three-dimensional protein structure maintenance, and an improved in-gel activity detection method developed by the research group, targeting respiratory chain complex I.
Neurodegenerative disease-induced motor and cognitive function impairments typically manifest after significant neuronal loss in the affected areas (e.g., dopaminergic neuron loss in the substantia nigra is less than 30%, as assessed by pathological and dopamine imaging studies), highlighting the need for early diagnostic methods. The findings of this study, concluding that mitochondrial function in peripheral blood leukocytes changes with the disease state, would possibly accelerate biomarker development to detect the signs of neuronal loss in the central nervous system.
Journal
The Journal of Biochemistry Online issue November 29, 2023 175, (2024), 289-298
Title:
Supercomplex formation of mitochondrial respiratory chain complexes in leukocytes from patients with neurodegenerative diseases
Authors:
Tsukasa Hara, Ryosuke Amagai, Ryuji Sakakibara, Ayako Okado-Matsumoto*
DOI No.:
10.1093/jb/mvad100