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Centrosome-Phagy Has Been Identifed

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Centrosome-Phagy Has Been Identifed Wu et al. Cell Biosci (2021) 11:49 https://doi.org/10.1186/s13578-021-00557-w Cell & Bioscience REVIEW Open Access Centrosome-phagy: implications for human diseases Qi Wu1†, Xin Yu1†, Le Liu2, Shengrong Sun1* and Si Sun3* Abstract Autophagy is a prominent mechanism to preserve homeostasis and the response to intracellular or extracellular stress. Autophagic degradation can be selectively targeted to dysfunctional subcellular compartments. Centrosome homeostasis is pivotal for healthy proliferating cells, but centrosome aberration is a hallmark of diverse human disor- ders. Recently, a process called centrosome-phagy has been identifed. The process involves a panel of centrosomal proteins and centrosome-related pathways that mediate the specifc degradation of centrosomal components via the autophagic machinery. Although autophagy normally mediates centrosome homeostasis, autophagy defects facili- tate ageing and multiple human diseases, such as ciliopathies and cancer, which beneft from centrosome aberration. Here, we discuss the molecular systems that trigger centrosome-phagy and its role in human disorders. Keywords: Centrosome, Autophagy, Ciliopathies, Aging, Cancer Centrosome composition and duplication distal region, so nine sets of microtubule doublets are Te centrosome is an evolutionarily conserved cylin- present there. Furthermore, in the proximal region, the drical organelle normally localized around the nuclei. A-microtubule of one triplet and the C-microtubule of It is composed of a pair of centrioles, which consist of the adjacent triplet are connected by an A–C linker [3]. fbres connecting their proximal ends and an amor- Other striking features present in mature centrioles are phous cloud of diferent proteins surrounding the cen- the subdistal and distal appendages. Te latter are essen- triole pair called pericentriolar material (Fig. 1a) (PCM) tial for docking beneath the plasma membrane upon [1]. A signature feature of the centriole is that nine sets templating the ciliary or fagellar axoneme [4]. Outside of microtubules are arranged in a radially symmetrical the centriole microtubule wall lies a cloud of proteins col- manner at the organelle periphery [2]. Te centriole is a lectively forming the PCM, which is critical for the nucle- polarized entity, with proximal and distal regions that dif- ation of cytoplasmic microtubules [5]. Another striking fer notably in the number of microtubules they harbour. nine-fold symmetrical structure is the cartwheel present Tus, nine microtubule triplets, dubbed the A-, B-, and in the proximal-most ~ 100 nm of the procentriole, which C-microtubules within each triplet, are present in the elongate and develop as the new daughter centriole prior proximal region. Te C-microtubule is absent from the to mitosis [6]. Te cartwheel can be observed before cen- triole microtubules during the assembly process in some systems and is essential for centriole biogenesis in most *Correspondence: [email protected]; [email protected] organisms [6], suggesting that it may impart the signa- † Qi Wu and Xin Yu contributed equally to this work ture nine-fold radial symmetry to the entire organelle. 1 Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, 238 Ziyang Road, Wuhan 430060, Hubei, People’s Republic Te PCM supplies sites for microtubule nucleation, thus of China determining the number and composition of microtu- 3 Department of Clinical Laboratory, Renmin Hospital of Wuhan bules during the cell cycle. Terefore, all microtubule- University, 238 Ziyang Road, Wuhan 430060, Hubei, People’s Republic of China related functions, including cell division, cell shape, Full list of author information is available at the end of the article © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Wu et al. Cell Biosci (2021) 11:49 Page 2 of 13 centrioles, which are linked through a fexible structure connecting their proximal ends [9]. Towards the G1-to- S transition, a procentriole starts to assemble ~ 100 nm away from the microtubule wall of the proximal region of each parental centriole, almost orthogonally to the wall. During the S and G2 phases, each procentriole remains engaged in this confguration with its parental centriole and elongates to ~ 400 nm. Towards the end of G2, the fexible link between the two parental centrioles is sev- ered, allowing the two centrosomes, each with a procen- triole/centriole pair, to separate and govern assembly of the bipolar mitotic spindle [10]. During mitosis, each procentriole disengages from its parental centriole and loses the cartwheel, which is likely targeted for degra- dation. Te two resulting centriolar cylinders in each daughter cell are then linked through their proximal ends via a fexible structure, thus completing the duplication cycle [9]. Together, these observations suggest that, in proliferating cells, the parental centriole provides a pref- erential scafold that somehow favours the local assembly of a single and correct procentriole, thus ensuring faithful centriole duplication [10]. Centrosome‑phagy contributes to centrosome homeostasis Centrosome homeostasis not only ensures the normality Fig. 1 Centrosome composition and duplication. a The centrosome of centrosome number and structure, but also maintains is composed of a pair of centrioles, which consist of fbres connecting the normal assembly process and function of centro- their proximal ends and PCM surrounding the centriole pair. Nine some, which is an essential factor for preserving cellu- microtubule triplets, dubbed the A-, B-, and C-microtubules within lar homeostasis and preventing disease onset [11]. And each triplet, are present in the proximal region of centrioles. The C-microtubule is absent from the distal region. In the proximal region, the deregulation of centrosome homeostasis is a hall- the A-microtubule and the C-microtubule are connected by an A–C mark feature of many human diseases [12]. Centrosome linker. Other striking features present in mature centrioles are the homeostasis is afected by many factors. For example, subdistal and distal appendages; b Cells in the G1 phase contain two nuclear pore complex (NPC)-associated proteins Nup133 centrioles termed the mother and daughter centrioles. Towards the and Nup358 (also known as RanBP2) are involved in the G1-to-S transition, a procentriole starts to assemble. During the S and G2 phases, each procentriole remains engaged in this confguration control of centrosome position, and their absence lead to with its parental centriole and elongates. Towards the end of G2, the the failure of centrosome tethering to the nucleus at the fexible link between the two parental centrioles is severed, allowing G2/M transition, which is required for timely establish- the two centrosomes to separate and govern assembly of the bipolar ment of a properly positioned mitotic spindle [13, 14]. mitotic spindle Overexpression or underexpression of some centrosome proteins like Polo-like kinase 4 (PLK4) and centrosomal P4.1 associated protein (CPAP, also known as Cenp- J) contribute to changes in the structure and quantity polarity, motility and adhesion, are coordinated by cen- of centrosomes [15, 16]. And electron transport chain trosomes [7]. dysfunction (mitochondrial DNA depletion or elec As with deoxyribonucleic acid (DNA) replication, the - duplication of the centrosome is semi-conservative and tron transport chain inhibition) [17], failure of cytoki- is coupled with cell cycle progression in most cases, thus nesis, mitotic slippage, cell–cell fusion and excessive ensuring that each cell is endowed with the accurate com- centrosome duplication can lead to centrosome amplif- plement of chromosomes and the correct number of two cation [18]. In addition, recent studies have shown that centrioles (Fig. 1b) [8]. During this process, the size of the autophagy is involved in regulating centrosome homeo- centrosome is strictly regulated. Cells in the G1 phase stasis [19–21]. contain two centrioles termed the mother and daughter Macroautophagy (hereafter referred to as autophagy) is a catabolic process. Te formation of a double membrane Wu et al. Cell Biosci (2021) 11:49 Page 3 of 13 phagophore (also known as an isolation membrane) is the maintaining the stability of centrosome [19]. Similarly, key to the process of autophagy. Tis membrane forms an centrosome amplifcation disorganized autophagosome autophagosome after it elongates and closes, engulfs cel- trafcking to lysosomes, resulting in an accumulation of lular
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