Abstract
Mitochondria are critical organelles that play a key role in cellular metabolism, survival, and homeostasis. Mitochondrial dysfunction has been implicated in the pathogenesis of diabetic kidney disease. The function of mitochondria is critically regulated by several mitochondrial protein kinases, including the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1). The focus of PINK1 research has been centered on neuronal diseases. Recent studies have revealed a close link between PINK1 and many other diseases including kidney diseases. This review will provide a concise summary of PINK1 and its regulation of mitochondrial function in health and disease. The physiological role of PINK1 in the major cells involved in diabetic kidney disease including proximal tubular cells and podocytes will also be summarized. Collectively, these studies suggested that targeting PINK1 may offer a promising alternative for the treatment of diabetic kidney disease.
Highlights
Mitochondria, the power generators of the cell, perform a wide range of cellular functions [1]
Under healthy and steady-state conditions, PINK1 is imported into the mitochondria by a positively charged N-terminal mitochondrial targeting sequences (MTS), via the presequence pathway, which is involved in the targeting of most matrix-localized proteins and some mitochondrial inner membrane (MIM)- and intra-membrane space (IMS)-localized proteins [8]
Palmitic acid (PA) induced increased expression of PINK1 and Parkin in podocytes, indicating that PINK1/Parkin-mediated mitophagy was activated in lipidinduced lipotoxicity, which was confirmed in the rat model of high fat diet (HFD)-induced obesity [71]
Summary
Mitochondria, the power generators of the cell, perform a wide range of cellular functions [1]. Maintenance of mitochondrial function and turnover is critical to cellular metabolism, survival, and homeostasis. Mitochondrial damage and dysregulation of turnover lead to metabolic dysfunction, oxidative stress, inflammation, and cell death, all of which are involved in the pathogenesis of diabetic kidney disease (DKD) [2]. Studies have shown that mitochondrial function is mainly regulated by mitochondrial protein kinases [4]. Activation of those mitochondrial protein kinases has emerged as an important molecular mechanism mediating the mitochondrial response to metabolic stresses in DKD. This review will provide a concise overview of PINK1 and explore its cellular function in healthy and damaged mitochondria as well as its physiological role in kidney cells primarily involved in the initiation and progression of DKD
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