Organelle asymmetry for proper fitness, function, and fate

Abstract

During cellular division, centrosomes are tasked with building the bipolar mitotic spindle, which partitions the cellular contents into two daughter cells. While every cell will receive an equal complement of chromosomes, not every organelle is symmetrically passaged to the two progeny in many cell types. In this review, we highlight the conservation of nonrandom centrosome segregation in asymmetrically dividing stem cells, and we discuss how the asymmetric function of centrosomes could mediate nonrandom segregation of organelles and mRNA. We propose that such a mechanism is critical for insuring proper cell fitness, function, and fate.

Fig. 1

Model of centrosome duplication. Centrosome duplication occurs in S-phase resulting in two centrosomes that are capable of organizing PCM in G2 (Callaini and Riparbelli 1990). a A cartoon representation of mammalian centriole duplication and mother–daughter centrosome formation. In early interphase, a cell receives a single centrosome containing a mother (M, with distal and subdistal appendages (Vorobjev and Chentsov 1980) and a daughter (D) centriole pair. In S-phase, the M–D disengaged centrioles each nucleate a granddaughter (GD) centriole to form a M-GD1 pair (mother centrosome) and a D-GD2 pair (daughter centrosome). The age of each centriole can be roughly calculated in units of cell cycles (cc). b Cultured Drosophila S2 cell in G2 stained for DNA (pink) and centrosomes (yellow). Mother–daughter identity is not actually known; the labeling is meant for illustration

Fig. 2

Centrosome inheritance patterns. The inheritance of the mother or daughter centrosome is highly dependent on cell type. Shown are four examples of this selective inheritance: a budding yeast, S. cerevisiae (Pereira et al. 2001), b Drosophila male germline stem cells (mGSCs; Yamashita et al. 2007), c Drosophila larval neural stem cells (NB; Conduit and Raff 2010; Januschke et al. 2011), and d mouse radial glia cells (RGC; Wang et al. 2009)

Fig. 3

Interphase MTOC asymmetry. a A cartoon illustrating a single interphase MTOC in each of four cell types. Supportive data does exist for budding yeast (Shaw et al. 1997), Drosophila male germline stem cells (mGSCs; Yamashita et al. 2007), and Drosophila larval neural stem cells (NBs; Januschke and Gonzalez 2010; Rebollo et al. 2007; Rusan and Peifer 2007). The mouse RGCs are not known to use such a mechanism. b Shows a summary of what little we know of the process of establishing MTOC asymmetry in interphase. The role of Kar9 in SPBs (Hotz et al. 2012; Liakopoulos et al. 2003; Miller and Rose 1998) and Centrobin in NBs (Januschke et al. 2013) are the best-characterized mechanisms thus far. Red text indicates all the hypotheses that need further investigation

Fig. 4

Asymmetric organelle inheritance. a Data from yeast suggest that both ER and mitochondria are selectively segregated into the mother cell or bud (Du et al. 2004; Lowe and Barr 2007; Peraza-Reyes et al. 2010). b A mammalian cell showing the sequestration of an aggresome into one of the two daughter cells following cell division. It has been proposed that an active mechanism is used to ensure the health of one cell at the expense of the other (Fuentealba et al. 2008; Rujano et al. 2006). c There has been much discussion as to why asymmetric centrosome activity might be needed in stem cells; proper spindle alignment and asymmetric division are the most common reasons given. Here, we would like to add to the discussion by speculating that another purpose for maintaining a more active MTOC in interphase is the segregation of different organelle pools. Although evidence does not exist for such a mechanism in Drosophila NBs, other systems suggest that this type of regulation is plausible in stem cells. We hypothesize that the stem cell (NB) and differentiated cell (GMC) need to inherit a different subset of ER, mitochondria, other organelles, and mRNA (not depicted) to properly perform their respective functions