Prohibitins in neurodegeneration and mitochondrial homeostasis

Abstract

The incidence of age-related neurodegenerative disorders has risen with the increase of life expectancy. Unfortunately, the diagnosis of such disorders is in most cases only possible when the neurodegeneration status is already advanced, and symptoms are evident. Although age-related neurodegeneration is a common phenomenon in living animals, the cellular and molecular mechanisms behind remain poorly understood. Pathways leading to neurodegeneration usually diverge from a common starting point, mitochondrial stress, which can serve as a potential target for early diagnosis and treatments. Interestingly, the evolutionarily conserved mitochondrial prohibitin (PHB) complex is a key regulator of ageing and metabolism that has been associated with neurodegenerative diseases. However, its role in neurodegeneration is still not well characterized. The PHB complex shows protective or toxic effects in different genetic and physiological contexts, while mitochondrial and cellular stress promote both up and downregulation of PHB expression. With this review we aim to shed light into the complex world of PHB’s function in neurodegeneration by putting together the latest advances in neurodegeneration and mitochondrial homeostasis associated with PHB. A better understanding of the role of PHB in neurodegeneration will add knowledge to neuron deterioration during ageing and help to identify early molecular markers of mitochondrial stress. This review will deepen our understanding of age-related neurodegeneration and provide questions to be addressed, relevant to human health and to improve the life quality of the elderly.

UBXN1 promotes liver tumorigenesis by regulating mitochondrial homeostasis

“…Notably, we revealed that UBXN1 interacts with the mitochondrial inner membrane protein PHB and maintains its expression, which is required for mitochondrial membrane integrity. PHB and PHB2 are evolutionarily conserved scaffold proteins that form a multimeric ring complex at the inner mitochondrial membrane that acts as a protein and lipid scaffold to ensure the function of the inner mitochondrial membrane [ 43 – 45 ]. Consistent with our observation, PHB deficiency disrupts the integrity of the mitochondrial membrane and triggers NOXA-mediated apoptosis in multiple myeloma cells [ 22 , 46 ].…”

Kamishoyosan and Kamikihito protect against decreased KCC2 expression induced by the P. gingivalis lipopolysaccharide treatment in PC-12 cells and improve behavioral abnormalities in male mice

“…PHB2 plays a protective role in many neurological defects, including neuroinflammation and cognitive function [ 29 , 30 ]. Our results show that the P. g LPS decreases KCC2 expression via the downregulation of PHB.…”