TOPICS
DATE
May 16, 2024
SHARE

May 16, 2024

Discovery of a Correlation Between Mitochondrial Respiratory Chain

Supercomplex Formation in Leukocytes and Disease Progression in Patients with Neurodegenerative Diseases
Dr.Ayako Okado-Matsumoto
A research group led by Associate Professor Ayako Okado-Matsumoto from the Department of Biology at Toho University, in collaboration with Professor Ryuji Sakakibara (at the time of the study) from the Department of Neurology at Toho University Medical Center Sakura Hospital, discovered that the formation of mitochondrial respiratory chain supercomplexes, encompassing energy production-related enzymes, in the peripheral blood leukocytes of patients with neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies) correlates with disease progression. These results were published online on November 29, 2023, in The Journal of Biochemistry and selected for the cover of the printed version (Vol. 175, Issue 3, 2024).
Dr. Ayako Okado-Matsumoto
A research group led by Associate Professor Ayako Okado-Matsumoto from the Department of Biology at Toho University, in collaboration with Professor Ryuji Sakakibara (at the time of the study) from the Department of Neurology at Toho University Medical Center Sakura Hospital, discovered that the formation of mitochondrial respiratory chain supercomplexes, encompassing energy production-related enzymes, in the peripheral blood leukocytes of patients with neurodegenerative diseases (such as Alzheimer’s disease, Parkinson’s disease, and dementia with Lewy bodies) correlates with disease progression. These results were published online on November 29, 2023, in The Journal of Biochemistry and selected for the cover of the printed version (Vol. 175, Issue 3, 2024).
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.
Key Points of the Announcement:
  • By improving a previously developed low-sensitivity detection method for mitochondrial respiratory chain complex I activity, the researchers could analyze the respiratory chain supercomplex formation in leukocytes using 161 peripheral blood leukocyte samples from patients with neurodegenerative diseases. Their results revealed a correlation between mitochondrial respiratory chain supercomplex formation and disease progression (Figure).
  • This study could potentially accelerate biomarker development, thereby helping elucidate cognitive and motor function-related neurodegenerative disease mechanisms and contributing to early diagnosis.
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

READ MORE RESEARCH NEWS - SCIENCE

@ Toho University