Parkinson’s disease (PD) is a heterogeneous, clinicopathologically defined neurodegenerative disorder, with an age-dependent incidence and a rapidly rising global prevalence1. More than 95% of affected individuals, in most populations, have idiopathic forms of PD (iPD), i.e., not of monogenic o...
However, with the progression of aristolochic acid nephropathy (AAN) in renal cortex, NDUFb8 level restored, while COX-1 level maintained low80. Similarly, the activity of respiratory complex 1, which is partly encoded by mtDNA, was more significantly impaired than that of respiratory complex II...
Mechanistic target of rapamycin complex 1 (mTORC1). A kinase that is part of the mTOR complex, which is a master regulator of anabolic biosynthesis. Liver ketogenesis Hepatic synthesis of ketone bodies, which is typically induced by fasting and provides tissues with fuel in low-nutrient conditions...
Mitochondrial diseases are chronic (long-term), genetic, often inherited disorders that occur when mitochondria fail to produce enough energy for the body to function properly. (Inherited means the disorder was passed on from parents to children.) Mitocho...
Deficiencies in the first complex (CI) of the OXPHOS system are most prevalent, and can be caused by a mutation in either mitochondrial or nuclear DNA [1]. CI deficiencies are associated with Leigh disease (LD), which has an incidence of approximately 1 in 77,000 live births [[2], [3...
Whole-exome sequencing identified a novel homozygous nonsense mutation inNDUFAF4(c.478G>T; p.Glu160Ter), encoding a mitochondrial complex I assembly factor. The disruptive effect of the mutation was corroborated by the absence of NDUFAF4 expression in patient fibroblasts. OXPHOS assembly studies ...
Mitochondrial metabolic disorder is one of the important pathogeneses of DCM [44], while Pdk4, Hmgcs2, Decr1, and Ivd are enzymes essential for mitochondrial metabolism. In DCM, the most significant metabolic disorders in myocardial tissues are decreased glucose utilization and increased fatty acid...
To better understand the mechanisms underlying their mitochondrial effects, fibrate actions on complex I of the respiratory chain and cell respiration were studied in vitro. In homogenates of rat skeletal muscle, fenofibrate, and to a lesser extent clofibrate, reduced the activity of complex I (10...
Because the major function of OSCP is to stabilize the F1FO complex by interacting with F1, we tried to further probe the association between OSCP loss-of-function and mPTP formation in neurons by disrupting the interaction of OSCP with F1. To this end, we downregulated the β-subunit, whic...
Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder without a cure. Here we show that mitochondrial respiratory chain complex I is an important small molecule druggable target in AD. Partial inhibition of complex I triggers the AMP-activated protein kinase-dependent signaling network...