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Review Article | Open Access

The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100864, PR China

Peer review under responsibility of Chongqing Medical University.

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Abstract

Mitochondrial autophagy (mitophagy) is the selective clearance of damaged or incomplete mitochondria by autophagy, which is critical for the functional integrity of the entire mitochondrial network and cell survival. Because dysfunction of mitophagy is closely related to many diseases, it is important to study the specific molecular mechanism and pathophysiological significance of mitophagy. FUN14 domain-containing 1 (FUNDC1) is a newly identified mitochondrial outer membrane protein that induces receptor-mediated mitophagy by its interaction with LC3 during hypoxia. The expression, phosphorylation, regulation and significance of FUNDC1 are reviewed in the context of a large number of pathophysiological conditions. Emerging evidence has demonstrated that levels and phosphorylation states of FUNDC1 are closely related to occurrence, progression and prognosis of various diseases including heart diseases and cancers, indicating that FUNDC1 may serve as a promising biomarker and potential therapeutic target.

Keywords

HypoxiaMitochondriaBiomarkerAutophagyPlateletsFUNDC1Heart diseasesMitochondrial ROS

References

1

Wallace DC. Mitochondrial genetic medicine. Nat Genet. 2018;50(12): 1642-1649.
Crossref Google Scholar
2

Mitchell P. Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev Camb Phil Soc. 1966;41: 445-502.
Crossref Google Scholar
3

Mitchell P. Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biochim Biophys Acta. 2011;1807(12): 1507-1538.
Crossref Google Scholar
4

Pickles S, Vigié P, Youle RJ. Mitophagy and quality control mechanisms in mitochondrial maintenance. Curr Biol. 2018;28(4): R170-R185.
Crossref Google Scholar
5

Gustafsson ÅB, Dorn GW 2nd. Evolving and expanding the roles of mitophagy as a homeostatic and pathogenic process. Physiol Rev. 2019;99(1): 853-892.
Crossref Google Scholar
6

Ney PA. Mitochondrial autophagy: Origins, significance, and role of BNIP3 and NIX. Biochim Biophys Acta. 2015;1853(10 Pt B): 2775-2783.
Crossref Google Scholar
7

Zhang W, Chen C, Wang J, Liu L, He Y, Chen Q. Mitophagy in cardiomyocytes and in platelets: a major mechanism of cardioprotection against ischemia/reperfusion injury. Physiology (Bethesda). 2018;33(2): 86-98.
Crossref Google Scholar
8

Zhang W, Ren H, Xu C, et al. Hypoxic mitophagy regulates mitochondrial quality and platelet activation and determines severity of I/R heart injury. Elife. 2016;5, e21407.
Crossref Google Scholar
9

Zhang W, Siraj S, Zhang R, Chen Q. Mitophagy receptor FUNDC1 regulates mitochondrial homeostasis and protects the heart from I/R injury. Autophagy. 2017;13(6): 1080-1081.
Crossref Google Scholar
10

Liu L, Feng D, Chen G, et al. Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced mitophagy in mammalian cells. Nat Cell Biol. 2012;14(2): 177-185.
Crossref Google Scholar
11

Gatica D, Lahiri V, Klionsky DJ. Cargo recognition and degradation by selective autophagy. Nat Cell Biol. 2018;20(3): 233-242.
Crossref Google Scholar
12

Ohsumi Y. Historical landmarks of autophagy research. Cell Res. 2014;24(1): 9-23.
Crossref Google Scholar
13

Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005;8(1): 3-5.
Crossref Google Scholar
14

Sarraf SA, Youle RJ. Parkin mediates mitophagy during beige-to-white fat conversion. Sci Signal. 2018;11(527), eaat1082.
Crossref Google Scholar
15

Pickrell AM, Youle RJ. The roles of PINK1, parkin, and mitochondrial fidelity in Parkinson's disease. Neuron. 2015;85(2): 257-273.
Crossref Google Scholar
16

Shirihai OS, Song M, Dorn GWII. How mitochondrial dynamism orchestrates mitophagy. Circ Res. 2015;116(11): 1835-1849.
Crossref Google Scholar
17

Schweers RL, Zhang J, Randall MS, et al. NIX is required for programmed mitochondrial clearance during reticulocyte maturation. Proc Natl Acad Sci U S A. 2007;104(49): 19500-19505.
Crossref Google Scholar
18

Murakawa T, Yamaguchi O, Hashimoto A, et al. Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. Nat Commun. 2015;6, e7527.
Crossref Google Scholar
19

Bhujabal Z, Birgisdottir AB, Sjøttem E, et al. FKBP8 recruits LC3A to mediate Parkin-independent mitophagy. EMBO Rep. 2017;18(6): 947-961.
Crossref Google Scholar
20

Wei Y, Chiang WC, , Mishra P, Levine B. Prohibitin 2 is an inner mitochondrial membrane mitophagy receptor. Cell. 2017;168(1-2): 224-238.
Crossref Google Scholar
21

Lee SH, Lee S, Du J, et al. Mitochondrial MsrB2 serves as a switch and transducer for mitophagy. EMBO Mol Med. 2019;11(8), e10409.
Crossref Google Scholar
22

Youle RJ, Narendra DP. Mechanisms of mitophagy. Nat Rev Mol Cell Biol. 2011;12(1): 9-14.
Crossref Google Scholar
23

Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7): 651-662.
Crossref Google Scholar
24

Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524(7565): 309-314.
Crossref Google Scholar
25

Kuang Y, Ma K, Zhou C, et al. Structural basis for the phosphorylation of FUNDC1 LIR as a molecular switch of mitophagy. Autophagy. 2016;12(12): 2363-2373.
Crossref Google Scholar
26

Lv M, Wang C, Li F, et al. Structural insights into the recognition of phosphorylated FUNDC1 by LC3B in mitophagy. Protein Cell. 2017;8(1): 25-38.
Crossref Google Scholar
27

Chen G, Han Z, Feng D, et al. A regulatory signaling loop comprising the PGAM5 phosphatase and CK2 controls receptor-mediated mitophagy. Mol Cell. 2014;54(3): 362-377.
Crossref Google Scholar
28

Wu W, Tian W, Hu Z, et al. ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 2014;15(5): 566-575.
Crossref Google Scholar
29

Wu H, Xue D, Chen G, et al. The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy. Autophagy. 2014;10(10): 1712-1725.
Crossref Google Scholar
30

Wang Z, Jiang H, Chen S, Du F, Wang X. The mitochondrial phosphatase PGAM5 functions at the convergence point of multiple necrotic death pathways. Cell. 2012;148(1-2): 228-243.
Crossref Google Scholar
31

Lee KH, Kang TB. The molecular links between cell death and inflammasome. Cells. 2019;8(9), e1057.
Crossref Google Scholar
32

Anderson MA, Huang D, Roberts A. Targeting BCL2 for the treatment of lymphoid malignancies. Semin Hematol. 2014;51(3): 219-227.
Crossref Google Scholar
33

Youle RJ, Strasser A. The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Biol. 2008;9(1): 47-59.
Crossref Google Scholar
34

McArthur K, Chappaz S, Kile BT. Apoptosis in megakaryocytes and platelets: the life and death of a lineage. Blood. 2018;131(6): 605-610.
Crossref Google Scholar
35

Strasser A, Vaux DL. Viewing BCL2 and cell death control from an evolutionary perspective. Cell Death Differ. 2018;25(1): 13-20.
Crossref Google Scholar
36

Wu S, Zou MH. Mitochondria-associated endoplasmic reticulum membranes in the heart. Arch Biochem Biophys. 2019;662: 201-212.
Crossref Google Scholar
37

Wu S, Lu Q, Wang Q, et al. Binding of FUN14 domain containing 1 with inositol 1,4,5-trisphosphate receptor in mitochondria-associated endoplasmic reticulum membranes maintains mitochondrial dynamics and function in hearts in vivo. Circulation. 2017;136(23): 2248-2266.
Crossref Google Scholar
38

Wu S, Lu Q, Ding Y, et al. Hyperglycemia-driven inhibition of AMP-activated protein kinase α2 induces diabetic cardiomyopathy by promoting mitochondria-associated endoplasmic reticulum membranes in vivo. Circulation. 2019;1399(16): 1913-1936.
Crossref Google Scholar
39

Guo R, Zong S, Wu M, Gu J, Yang M. Architecture of human mitochondrial respiratory megacomplex I2III2IV2. Cell. 2017;170(6): 1247-1257.
Crossref Google Scholar
40

Wang X, Zhang X, Wu D, et al. Mitochondrial flashes regulate ATP homeostasis in the heart. Elife. 2017;6, e23908.
Crossref Google Scholar
41

Zhou H, Zhu P, Wang J, Zhu H, Ren J, Chen Y. Pathogenesis of cardiac ischemia reperfusion injury is associated with CK2α-disturbed mitochondrial homeostasis via suppression of FUNDC1-related mitophagy. Cell Death Differ. 2018;25(6): 1080-1093.
Crossref Google Scholar
42

Zhou H, Zhu P, Guo J, et al. Ripk3 induces mitochondrial apoptosis via inhibition of FUNDC1 mitophagy in cardiac IR injury. Redox Biol. 2017;13: 498-507.
Crossref Google Scholar
43

Zhou H, Li D, Zhu P, et al. Melatonin suppresses platelet activation and function against cardiac ischemia/reperfusion injury via PPARγ/FUNDC1/mitophagy pathways. J Pineal Res. 2017;63, e12438.
Crossref Google Scholar
44

Boengler K, Schlüter KD, Schermuly RT, Schulz R. Cardioprotection in right heart failure. Br J Pharmacol. 2020;177(23): 5413-5431.
Crossref Google Scholar
45

Mitchell MB, Winter CB, Banerjee A, Harken AH. The relationship between ischemia-reperfusion injury, myocardial stunning and cardiac preconditioning. Surg Gynecol Obstet. 1993;177(1): 97-114.
Google Scholar
46

Ippolito L, Giannoni E, Chiarugi P, Parri M. Mitochondrial redox hubs as promising targets for anticancer therapy. Front Oncol. 2020;10, e256.
Crossref Google Scholar
47

Zhang T, Suo C, Zheng C, Zhang H. Hypoxia and metabolism in metastasis. Adv Exp Med Biol. 2019;1136: 87-95.
Crossref Google Scholar
48

Ast T, Meisel JD, Patra S, et al. Hypoxia rescues frataxin loss by restoring iron sulfur cluster biogenesis. Cell. 2019;177(6): 1507-1521.
Crossref Google Scholar
49

Sprenger HG, Langer T. The good and the bad of mitochondrial breakups. Trends Cell Biol. 2019;29(11): 888-900.
Crossref Google Scholar
50

Lee P, Chandel NS, Simon MC. Cellular adaptation to hypoxia through hypoxia inducible factors and beyond. Nat Rev Mol Cell Biol. 2020;21(5): 268-283.
Crossref Google Scholar
51

Chen Z, Liu L, Cheng Q, et al. Mitochondrial E3 ligase MARCH5 regulates FUNDC1 to fine-tune hypoxic mitophagy. EMBO Rep. 2017;18(3): 495-509.
Crossref Google Scholar
52

Yuan Q, Sun N, Zheng J, et al. Prognostic and immunological role of FUN14 domain containing 1 in pan-cancer: friend or foe? Front Oncol. 2020;9, e1502.
Crossref Google Scholar
53

Li W, Li Y, Siraj S, et al. FUN14 domain-containing 1-mediated mitophagy suppresses hepatocarcinogenesis by inhibition of inflammasome activation in mice. Hepatology. 2019;69(2): 604-621.
Crossref Google Scholar
54

Wu L, Zhang D, Zhou L, et al. FUN14 domain-containing 1 promotes breast cancer proliferation and migration by activating calcium-NFATC1-BMI1 axis. EBioMedicine. 2019;41: 384-394.
Crossref Google Scholar
55

Hou H, Er P, Cheng J, et al. High expression of FUNDC1 predicts poor prognostic outcomes and is a promising target to improve chemoradiotherapy effects in patients with cervical cancer. Cancer Med. 2017;6(8): 1871-1881.
Crossref Google Scholar
56

Hui L, Wu H, Wang TW, Yang N, Guo X, Jang XJ. Hydrogen peroxide-induced mitophagy contributes to laryngeal cancer cells survival via the upregulation of FUNDC1. Clin Transl Oncol. 2019;21(5): 596-606.
Crossref Google Scholar
57

Roperto S, Russo V, De Falco F, Rosati A, Catoi C, Roperto F. FUNDC1-mediated mitophagy in bovine papillomavirus-infected urothelial cells. Vet Microbiol. 2019;234: 51-60.
Crossref Google Scholar
58

Yan M, Yu Y, Mao X, et al. Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner. Int Immunopharm. 2019;71: 61-67.
Crossref Google Scholar
59

Cai Q, Jeong YY. Mitophagy in alzheimer's disease and other age-related neurodegenerative diseases. Cells. 2020;9(1), e150.
Crossref Google Scholar
60

Chan DC. Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol. 2020;15: 235-259.
Crossref Google Scholar
61

Paik DT, Cho S, Tian L, Chang HY, Wu JC. Single-cell RNA sequencing in cardiovascular development, disease and medicine. Nat Rev Cardiol. 2020;17(8): 457-473.
Crossref Google Scholar
62

Xie Q, Faust K, Van Ommeren R, Sheikh A, Djuric U, Diamandis P. Deep learning for image analysis: personalizing medicine closer to the point of care. Crit Rev Clin Lab Sci. 2019;56(1): 61-73.
Crossref Google Scholar
63

Long KB, Young RM, Boesteanu AC, et al. CAR T cell therapy of non-hematopoietic malignancies: detours on the road to clinical success. Front Immunol. 2018;9, e2740.
Crossref Google Scholar
64

Horwitz RI, Charlson ME, Singer BH. Medicine based evidence and personalized care of patients. Eur J Clin Invest. 2018;48, e12945.
Crossref Google Scholar
65

Wang Q, Lv H, Lu L, Ren P, Li LJ. Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury. Matern Fetal Neonatal Med. 2019;32(21): 3685-3692.
Crossref Google Scholar
66

Sabbah HN. Targeting the mitochondria in heart failure: a translational perspective. JACC Basic Transl Sci. 2020;5(1): 88-106.
Crossref Google Scholar
67

Chiarelli R, Martino C, Roccheri MC. Cadmium stress effects indicating marine pollution in different species of sea urchin employed as environmental bioindicators. Cell Stress Chaperones. 2019;24(4): 675-687.
Crossref Google Scholar
68

Rogov VV, Suzuki H, Marinković M, et al. Phosphorylation of the mitochondrial autophagy receptor Nix enhances its interaction with LC3 proteins. Sci Rep. 2017;7(1), e1131.
Crossref Google Scholar
69

Zhang W, Ma Q, Siraj S, et al. Nix-mediated mitophagy regulates platelet activation and life span. Blood Adv. 2019;3(15): 2342-2354.
Crossref Google Scholar
Genes & Diseases
Volume 8 Issue 5,
September 2021
Pages 640-654
DOI: 10.1016/j.gendis.2020.08.011
Cite this article:
Zhang W. The mitophagy receptor FUN14 domain-containing 1 (FUNDC1): A promising biomarker and potential therapeutic target of human diseases. Genes & Diseases, 2021, 8(5): 640-654. https://doi.org/10.1016/j.gendis.2020.08.011

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Received: 28 April 2020
Revised: 22 August 2020
Accepted: 26 August 2020
Published: 02 September 2020
© 2020, Chongqing Medical University. Production and hosting by Elsevier B.V.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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