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They Might Cut It-Lysosomes and Autophagy in Mitotic Progression

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.727538

Keywords

autophagy; cathepsin B; chromosome segregation; lysosome; mitosis; spindle

Funding

  1. European Research Council [AdG340751]
  2. Danish National Research Foundation [DNRF125]
  3. Danish Cancer Society [R269-A15695]
  4. Novo Nordisk Foundation [NNF15OC0018914]
  5. Danish Council for Independent Research [DFF-7016-00360]

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Mitosis, a tightly regulated process in mammalian life, can still result in errors leading to chromosomal instabilities and malignancies. Recent discoveries have shown unexpected roles for autophagy and lysosomes in preserving genomic integrity during mitosis.
The division of one cell into two looks so easy, as if it happens without any control at all. Mitosis, the hallmark of mammalian life is, however, tightly regulated from the early onset to the very last phase. Despite the tight control, errors in mitotic division occur frequently and they may result in various chromosomal instabilities and malignancies. The flow of events during mitotic progression where the chromosomes condensate and rearrange with the help of the cytoskeletal network has been described in great detail. Plasma membrane dynamics and endocytic vesicle movement upon deadhesion and reattachment of dividing cells are also demonstrated to be functionally important for the mitotic integrity. Other cytoplasmic organelles, such as autophagosomes and lysosomes, have until recently been considered merely as passive bystanders in this process. Accordingly, at the onset of nuclear envelope breakdown in prometaphase, the number of autophagic structures and lysosomes is reduced and the bulk autophagic machinery is suppressed for the duration of mitosis. This is believed to ensure that the exposed nuclear components are not unintentionally delivered to autophagic degradation. With the evolving technologies that allow the detection of subtle alterations in cytoplasmic organelles, our understanding of the small-scale regulation of intracellular organelles has deepened rapidly and we discuss here recent discoveries revealing unexpected roles for autophagy and lysosomes in the preservation of genomic integrity during mitosis.

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