期刊
FRONTIERS IN PHYSIOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphys.2021.715485
关键词
protein aggregates; autosomal dominant mutation; peroxisome; inflammasome; renal fibrosis; mitochondrial damage associated molecular patterns
类别
资金
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [387509280, SFB 1350]
The mitochondria in the proximal tubule play a crucial role in providing energy, affecting renal function in diverse ways. Two autosomal dominantly inherited forms of renal Fanconi syndrome highlight the multifaceted nature of mitochondrial pathology. Mutations in enzymes of fatty acid metabolism or creatine biosynthesis pathway can lead to distinct pathophysiological mechanisms, demonstrating the spectrum of proximal tubular mitochondrial diseases.
The mitochondria of the proximal tubule are essential for providing energy in this nephron segment, whose ATP generation is almost exclusively oxygen dependent. In addition, mitochondria are involved in a variety of metabolic processes and complex signaling networks. Proximal tubular mitochondrial dysfunction can therefore affect renal function in very different ways. Two autosomal dominantly inherited forms of renal Fanconi syndrome illustrate how multifaceted mitochondrial pathology can be: Mutation of EHHADH, an enzyme in fatty acid metabolism, results in decreased ATP synthesis and a consecutive transport defect. In contrast, mutations of GATM, an enzyme in the creatine biosynthetic pathway, leave ATP synthesis unaffected but do lead to mitochondrial protein aggregates, inflammasome activation, and renal fibrosis with progressive renal failure. In this review article, the distinct pathophysiological mechanisms of these two diseases are presented, which are examples of the spectrum of proximal tubular mitochondrial diseases.
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