The functional role of Higd1a in mitochondrial homeostasis and in multiple disease

Higd1a is a conserved gene in evolution which is widely expressed in many tissues in mammals.Accumulating evidence has revealed multiple functions of Higd1a,as a mitochon-drial inner membrane protein,in the regulation of metabolic homeostasis.It plays an impor-tant role in anti-apoptosis and promotes cellular survival in several cell types under hypoxic condition.And the survival of porcine Sertoli cells facilitated by Higd1a helps to support repro-duction.In some cases,Higd1a can serve as a sign of metabolic stress.Over the past several years,a considerable amount of studies about how tumor fate is determined and how cancerous proliferation is regulated by Higd1a have been performed.In this review,we summarize the physiological functions of Higd1a in metabolic homeostasis and its pathophysiological roles in distinct diseases including cancer,nonalcoholic fatty liver disease(NAFLD),type Il diabetes and mitochondrial diseases.The prospect of Higd1a with potential to preserve mammal health is also discussed.This review might pave the way for Higd1a-based research andapplicationinclinicalpractice.

Cysteine dioxygenase type 1 (CDO1): Its functional role in physiological and pathophysiological processes

Cysteine dioxygenase type 1 (CDO1), belonging to the mammalian non-heme Fe(II) dioxygenases family, is a key enzyme for cysteine catabolism. Its activity and expression is regulated through multiple mechanisms. CDO1 is involved in a spectrum of physiological processes including lipid metabolism, adipogenesis, osteoblastic differentiation, redox homeostasis, fertility, bile acid metabolism, sulfide metabolism, and organismal growth and development. Many of these processes are regulated directly or indirectly by CDO1-mediated metabolism of cysteine. In pathophysiological processes, the degree of CDO1 promoter methylation is closely related to the progression and malignancy of tumors, and overexpression of CDO1 will promote ferroptosis of cancer cells. Moreover, CDO1 may ameliorate metabolic disorders through the taurine-mediated improvement of lipid metabolism and insulin sensitivity and improve neurodegenerative diseases by regulating cysteine level. Therefore, elucidation of the mechanisms underlying the role of CDO1 would provide a clearer view of the therapeutic potential and possible risks of targeting this important enzyme.

Krüppel-like factor 10 (KLF10) as a critical signaling mediator: Versatile functions in physiological and pathophysiological processes

Krüppel-like factor 10 (KLF10), also known as TGFβ-inducible early gene-1 (TIEG1), was first found in human osteoblasts. Early studies show that KLF10 plays an important role in osteogenic differentiation. Through decades of research, KLF10 has been found to have complex functions in many different cell types, and its expression and function is regulated in multiple ways. As a downstream factor of transforming growth factor β (TGFβ)/SMAD signaling, KLF10 is involved in various biological functions, including glucose and lipid metabolism in liver and adipose tissue, the maintenance of mitochondrial structure and function of the skeletal muscle, cell proliferation and apoptosis, and plays roles in multiple disease processes, such as nonalcoholic steatohepatitis (NASH) and tumor. Besides, KLF10 shows gender-dependent difference of regulation and function in many aspects. In this review, the biological functions of KLF10 and its roles in disease states is updated and discussed, which would provide new insights into the functional roles of KLF10 and a clearer view of potential therapeutic strategies by targeting KLF10.