Organelle Inheritance Control of Mitotic Entry and Progression: Implications for Tissue Homeostasis and Disease

Abstract

The Golgi complex (GC), in addition to its well-known role in membrane traffic, is also actively involved in the regulation of mitotic entry and progression. In particular, during the G2 phase of the cell cycle, the Golgi ribbon is unlinked into isolated stacks. Importantly, this ribbon cleavage is required for G2/M transition, indicating that a “Golgi mitotic checkpoint” controls the correct segregation of this organelle. Then, during mitosis, the isolated Golgi stacks are disassembled, and this process is required for spindle formation. Moreover, recent evidence indicates that also proper mitotic segregation of other organelles, such as mitochondria, endosomes, and peroxisomes, is required for correct mitotic progression and/or spindle formation. Collectively, these observations imply that in addition to the control of chromosomes segregation, which is required to preserve the genetic information, the cells actively monitor the disassembly and redistribution of subcellular organelles in mitosis. Here, we provide an overview of the major structural reorganization of the GC and other organelles during G2/M transition and of their regulatory mechanisms, focusing on novel findings that have shed light on the basic processes that link organelle inheritance to mitotic progression and spindle formation, and discussing their implications for tissue homeostasis and diseases.

Cubic Membranes Formation in Synchronized Human Hepatocellular Carcinoma Cells Reveals a Possible Role as a Structural Antioxidant Defense System in Cell Cycle Progression

“…emergence of CMs, suggesting that the enhanced mitochondrial function (providing energy for mitosis) in G2 phase may lead to the increase in ROS level and the subsequent CMs formation. Accumulating evidence suggests that mitochondrial function has a dynamic change in cell cycle (Owusu-Ansah et al, 2008;Horbay and Bilyy, 2016;Mascanzoni et al, 2019), and ATP production is much more dependent on mitochondrial respiration in G2/M phase of cell cycle (Bao et al, 2013). This may be due to cell cycle machinery cyclin B1/Cdk1, which localized to the matrix of mitochondria and phosphorylated a cluster of mitochondrial proteins, and eventually resulted in the enhanced mitochondrial respiration and ATP generation in G2 phase (Wang et al, 2014).…”

A cell cycle checkpoint for the endoplasmic reticulum

“…When a eukaryotic cell undergoes division, it faces the challenge of generating genetically identical daughter cells (Ciccia and Elledge, 2010;Matellan and Monje-Casas, 2020;Musacchio and Desai, 2017). The cell must copy the entire genome-which consists of over three billion base pairs in human-without making major mistakes.…”

“…This framework allows cellular functions to fine-tune themselves discretely, but also requires these organelles to be divided during cell division. In contrast to genome replication and separation, however, we know relatively little about the rules that govern the division of cytoplasmic components or organelles (Mascanzoni et al, 2019;Vevea et al, 2014;Weisman, 2003). Historically, almost all cell division studies have focused on issues associated with the genome and the cell cycle checkpoints ensuring that all dividing cells end up with completely and accurately replicated DNA.…”

Robust classification of cell cycle phase and biological feature extraction by image-based deep learning

“…For example, DNA is replicated during S phase, resulting in a doubling of chromatin content and the concordant regulation of nuclear size ( Webster et al , 2009 ; Mukherjee et al , 2016 ). Organelles such as the Golgi apparatus and endoplasmic reticulum also have cell cycle-dependent dynamics in number or size to align with mitotic distribution and inheritance ( Lowe and Barr, 2007 ; Mascanzoni et al , 2019 ). At the molecular level, the architecture of cytoskeletal components such as microtubule and actin filaments has marked cell cycle phase dynamics ( Champion et al , 2017 ; Jones et al , 2019 ).…”