Table 1.

The core components of Hippo pathway affect various disorders via autophagy.

Author, year	Disorders	Experimental models	Effector cell	Effects
Zhang et al.45 Lin et al.138 You et al.139	DCM	Streptozotocin induce experimental diabetes in mice	CMEC/cardiomyocyte	MST1 knockdown upregulated autophagy and prevented apoptosis in cardiomyocytes and CMEC.
Shi et al.140	DCM	Streptozotocin constructed diabetic model in endothelium-specific MST1 Tg mice	CMEC/cardiomyocyte	The MST1-enriched exosomes released from CMECs inhibit autophagy and glucose metabolism, thereby promote apoptosis in cardiomyocyte.
Yuan et al.141	Atherosclerosis	ApoE−/− mice	HUVECs	Laminar flow protects the endothelium, inhibits Hippo-YAP signaling by promoting endothelial autophagy and SIRT1 expression, and blocks the formation of atherosclerotic plaques.
Wang et al.142	Atherosclerosis	ApoE−/−: Mst1−/− and ApoE−/−: Mst1 Tg mice	Murine macrophage	In ApoE (−/−) mice, MST1 may stabilize atherosclerotic plaques by inhibiting macrophage autophagy and promoting macrophage apoptosis.
Shang et al.143	Septic cardiomyopathy	Lipopolysaccharide (LPS)-induced septic cardiomyopathy MST1−/− mice	Cardiomyocyte	Septic cardiomyopathy is characterized with MST1 upregulation and deletion of MST1-activated mitophagy, thereby attenuated LPS-mediated mitochondrial damage.
Yu et al.144	Cardiac I/R injury	Mst1−/− mice	Cardiomyocyte	MST1 deficiency activates protective mitophagy, thereby reducing cardiomyocyte mitochondrial apoptosis and regulating mitochondrial homeostasis.
Yao et al.145	Hypertension	Infusion of Ang II induces hypertension in mice	HUVECs	In endothelial cells, mTORC1 regulates autophagy-dependent YAP degradation and controls blood pressure via COX-2/mPGES-1/PGE 2 cascade.
Lee et al.146	ALS	ALS mouse model	Mouse motor neuron-like NSC34 cells	The activation of MST1 by SOD1 leads to autophagosome accumulation and blocking autophagy flux, which contribute to the demise of motor neurons both in vitro and in vivo.
Zhang et al.147	SCI	MST1−/− and MST1 Tg SCI-induction mice	—	MST1 deficiency promotes posttraumatic spinal motor neuron survival via enhancement of autophagy flux.
Hsu et al.98	Barth syndrome	—	MEFs	TAZ deficiency in MEFs caused defective mitophagosome biogenesis (the mitophagy in mitochondria quality control) and leads to impaired oxidative phosphorylation and oxidative stress.
Liang et al.70	TSC	TSC mouse model	Mouse embryonic fibroblast	YAP is upregulated by mTOR in mouse and human perivascular epithelioid cell tumors (PEComas), and autophagy impairs YAP degradation in TSC-deficient cells, suggesting that the regulatory effects of YAP by mTOR and autophagy are therapeutic targets.
Xiao et al.148	Doxorubicin-induced cardiotoxicity	DOX-induced cardiotoxicity model in mice	Rat cardiomyocytes	YAP/Parkin pathway presented DOX-induced cardiotoxicity in mouse heart by enhancing mitophagy.
Zhou et al.149	NAFLD	MST1−/− and MST1 WT NAFLD mouse model	Mouse primary hepatocytes	MST1 deletion reversed Parkin-related mitophagy, suppressed hepatocyte mitochondrial stress, prevented diet-induced NAFLD.
Li et al.49	HCC	Induction of HCC by intraperitoneal injection of diethylamine (DEN) in wild-type and RASSF1A-knockout mice.	Mouse primary hepatocytes	RASSF1A inhibits PI3K-AKT-mTOR pathway through MST1 to enhance autophagic flux, further inhibiting HCC and improving survival.
Li et al.92	HCC	Induction of HCC by intraperitoneal injection of diethylamine (DEN) in wild-type and liver-specific LRPPRC-knockout mice.	Mouse primary hepatocytes	LRPPRC acts through YAP-P27 to control cell ploidy and P62 hence regulating autophagy maturation.
Lee et al.88	HCC	Liver-specific Atg7-knockout mice Atg7/YAP double-knockout mice	The murine and human hepatocyte lines	Atg7 knockdown suppressed autophagy and YAP nuclear localization. YAP acts as an autophagic substrate in liver differentiation and carcinogenesis.
Liu et al.150	PTC	Clinical thyroid papillary carcinoma tissue microarray analysis	PTC cell lines	In papillary thyroid cancer, YAP expression correlates with clinicopathological parameters. In vitro, YAP inhibits autophagy but enhances cell proliferation.
Li et al.151	Breast cancer	Human breast tissue microarray; MCF-7 cells were subcutaneously injected into BALB/c athymic nude mice	Breast cell line and breast cancer cell line	HBXIP inhibits MST1 acetylation, leading to autophagy-dependent degradation of MST1, HBXIP-mediated reduction of tumor suppressor MST1 promotes the growth of breast cancer cells in vitro and in vivo.
Yan et al.69	Gastric cancer	—	Normal gastric mucosal cell line and gastric cancer cell line	Knockdown of YAP causes mitochondrial apoptosis and cellular oxidative stress, which subsequently inhibits mitophagy, cancer cell survival, and migration.
Wang et al.89	Lung cancer	Lung cancer and adjacent normal tissues	Lung cancer cell line	Aurora A upregulates YAP expression by blocking autophagy and Aurora A kinase expression is positively correlated with YAP.
Zhang et al.152	Esophageal cancer	—	Esophageal cancer cell line	MST1 overexpression inhibits mitophagy activity, augments IL-24-induced esophageal cancer death via enhanced mitochondrial stress.
Fan et al.153	Multiple myeloma	PINK1-knockout mice and C57BL/6 WT controls Myeloma xenograft mouse model	Multiple myeloma cell line	Activation of PINK1-dependent mitophagy inhibits migration, suppresses myeloma cell homing to calvarium, and decreases osteolytic bone lesions via the MOB1B-mediated Hippo-YAP/TAZ pathway.
Hu et al.154	Pancreatic cancer	—	Normal ductal epithelial cell line and pancreatic cancer cell line	MST1 upregulation regulates pancreatic cancer cell apoptosis through mitofusin 2 (Mfn2)‑mediated mitophagy.
Wei et al.155	Colorectal cancer	Colorectal cancer xenograft mouse model	Colorectal cancer cell line	FAT4 suppresses colorectal cancer by promoting autophagy and inhibiting the epithelial-to-mesenchymal transition (EMT).

ALS amyotrophic lateral sclerosis, ApoE−/− apolipoprotein E-deficient, CMEC cardiac microvascular endothelial cell, DCM diabetic cardiomyopathy, HBXIP hepatitis B Virus X interacting protein, HCC hepatocellular carcinoma, HUVECs human umbilical vein endothelial cells, I/R ischemia-reperfusion, MEFs primary mouse embryonic fibroblasts, MST1^−/− MST1 knockout, MST1 Tg MST1 transgenic, NAFLD non-alcoholic fatty liver disease, PINK1 PTEN-induced putative kinase 1, PTC papillary thyroid carcinoma, SCI spinal cord injury, SOD1 superoxide dismutase 1, TSC tuberous sclerosis complex, WT wild type.