Recent progress in understanding mitokines as diagnostic and therapeutic targets in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is one of the most prevalent tumors worldwide and the leading contributor to cancer-related deaths.The progression and metastasis of HCC are closely associated with altered mitochondrial metabolism,including mitochondrial stress response.Mitokines,soluble proteins produced and secreted in response to mitochondrial stress,play an essential immunomodulatory role.Immunotherapy has emerged as a crucial treatment option for HCC.However,a positive response to therapy is typically dependent on the interaction of tumor cells with immune regulation within the tumor microenvironment.Therefore,exploring the specific immunomodulatory mechanisms of mitokines in HCC is essential for improving the efficacy of immunotherapy.This study provides a comprehensive overview of the association between HCC and the immune microenvironment and highlights recent progress in understanding the involvement of mitochondrial function in preserving liver function.In addition,a systematic review of mitokines-mediated immunomodulation in HCC is presented.Finally,the potential diagnostic and therapeutic roles of mitokines in HCC are prospected and summarized.Recent progress in mitokine research represents a new prospect for mitochondrial therapy.Considering the potential of mitokines to regulate immune function,investigating them as a relevant mole cular target holds great promise for the diagnosis and treatment of HCC.

Inter-tissue communication of mitochondrial stress and metabolic health

Mitochondria function as a hub of the cellular metabolic network.Mitochondrial stress is closely associated with aging and a variety of diseases,including neurodegeneration and cancer.Cells autonomously elicit specific stress responses to cope with mitochondrial stress to maintain mitochondrial homeostasis.Interestingly,mitochondrial stress responses may also be induced in a non-autonomous manner in cells or tissues that are not directly experiencing such stress.Such non-autonomous mitochondrial stress responses are mediated by secreted molecules called mitokines.Due to their significant translational potential in improving human metabolic health,there has been a surge in mitokine-focused research.In this review,we summarize the findings regarding inter-tissue communication of mitochondrial stress in animal models.In addition,we discuss the possibility of mitokine-mediated intercellular mitochondrial communication originating from bacterial quorum sensing.