Biology subjects

Nosrati, R.

Publications and source records attributed to Nosrati, R..

4 recordsLinked to original sources

bioRxiv2026

Chromatin- and actin-mediated mitochondrial streaming leads to patterning of mitochondrial distribution in oocytes

Mitochondria are highly dynamic organelles, and their spatiotemporal organization is strictly regulated. While it has long been recognized that mitochondria in ovulated oocytes are concentrated in the spindle hemisphere, the mechanism remains unknown. Through live cell imaging and modelling, we have discovered three features of mitochondrial dynamics in the ooplasm: (i) actin-driven cortical mitochondrial streaming is delimited to the boundary of the polarized spindle hemisphere; (ii) distinct from bulk cytoplasmic streaming, mitochondrial streaming occurs bilaterally and perpendicular to the long axis of the MII spindle and, (iii) mitochondria movement from the cytoplasm to the polarized cortex is via MYO19-mediated chromatin-associated channel around the spindle midzone. This directionality in mitochondrial streaming patterns the ooplasm of the spindle cortex, creating mitochondria-rich and mitochondria-poor regions. These features explain the establishment of the polar gradient of mitochondria in MII oocytes and may provide new insight into the spatiotemporal organization of mitochondria in cells.

cell biology↗

bioRxiv2024

A novel CCDC112-dependent process of sperm midpiece formation and epididymal maturation

The sperm mitochondrial sheath has proposed functions in structural support and energy production for motility. Here we define coiled coil domain containing protein 112, CCDC112, as crucial for male fertility, specifically in the assembly and function of the mitochondrial sheath. We unveiled a previously unrecognised process of epididymal mitochondrial sheath maturation. Sperm mitochondrial sheaths are structurally immature upon exiting the testis and continue to mature as they transit from the caput to the cauda epididymis. Data reveal the critical role of CCDC112 in mitochondrial morphogenesis during sheath formation. A lack of CCDC112 lead to significantly reduced mitochondrial respiration capacity, irregular flagellar waveforms, diminished progressive motility and a failure of sperm to traverse the female reproductive tract to the site of fertilisation and penetrate the zonae pellucidae of oocytes. Finally, we identify CCDC112 as a component of the distal appendages of the mother centriole and identify a facilitative role in core tail assembly. Collectively, CCDC112 is a key regulator of sperm mitochondrial sheath assembly while further expanding the understanding of spermatogenesis, energy generation and flagella kinematics.

developmental biology↗

bioRxiv2024

Elastohydrodynamic mechanisms govern beat pattern transitions in eukaryotic flagella

Eukaryotic cilia and flagella exhibit complex beating patterns that change depending on environmental conditions such as fluid viscosity. The mechanism behind these beat pattern transitions remains unclear, although they are thought to arise from changes in the internal forcing provided by the axoneme. We show here that such transitions may arise universally across species via an elastohydrodynamic mechanism. We perform simulations of inextensible and unshearable but twistable Kirchhoff rods driven internally by a travelling bending-moment wave in a fixed plane in the material frame of the rods. We show that, for a large range of beating amplitudes and frequencies, the internally planar driving wave results in the growth of twist perturbations. Outside this domain, the driving leads to simple planar waveforms. Within the non-planar domain, we observe quasiplanar, helical, and complex - perhaps chaotic - beating patterns. The transitions between these states depend quantitatively on physical parameters such as the internal forcing, flagellum stiffness and length, viscosity of the ambient medium, or the presence of a plane wall. Beat pattern transitions in our simulations can be mapped to similar transitions observed in bull and sea urchin sperm when the medium viscosity is varied. Comparison of the simulation results with experimentally observed transitional viscosities in our experiments and elsewhere suggests an assay whereby one can estimate the average force exerted by dynein motors. This could potentially lead to diagnostic assays measuring the health of sperm based on their beating pattern. Significance StatementThe ability of flagella and cilia to manipulate their beating waveforms in different physical environments has important implications for human and animal health. Beat transitions in mammalian sperm flagella, for example, may help sperm navigate the complex reproductive tract to reach the egg. Abnormal beating behaviour, which may have a range of unknown underlying causes, can result in ciliopathies and reproductive disorders. This work provides insight into the physical origins of beat transitions in flagella and shows how they depend quantitatively on flagellum stiffness and length, internal driving provided by the axoneme, viscosity of the ambient medium, and the presence of a plane wall. This could allow one to diagnose the root cause of an abnormal flagellar beat and thus design appropriate treatment.

biophysics↗

bioRxiv2020

Flagellar energetics from high-resolution imaging of beating patterns in tethered mouse sperm

While much is known about the microstructure of sperm flagella, the mechanisms behind the generation of flagellar beating patterns by the axoneme are still not fully understood. We demonstrate a technique for investigating the energetics of flagella or cilia. We record the planar beating of tethered wildtype and Crisp2-knockout mouse sperm at high-speed and high-resolution and extract centerlines using digital image processing techniques. We accurately reconstruct beating waveforms using a Chebyshev-polynomial based Proper Orthogonal Decomposition of the centerline tangent-angle profiles. External hydrodynamic forces and the internal resistance from the passive flagellar material are calculated from the observed kinematics of the beating patterns using a Soft, Internally-Driven Kirchhoff-Rod (SIDKR) model. Energy conservation is employed to further compute the flagellar energetics. We thus obtain the distribution of mechanical power exerted by the dynein motors without any further assumptions about mechanisms regulating axonemal function. We find that, in both the mouse genotypes studied, a large proportion of the mechanical power exerted by the dynein motors is dissipated internally, within the passive structures of the flagellum and by the motors themselves. This internal dissipation is considerably greater than the hydrodynamic dissipation in the aqueous medium outside. The net power input from the dynein motors in sperm from Crisp2-knockout mice is significantly smaller than in corresponding wildtype samples. The reduced power is correlated with slower beating and smaller amplitudes. These measurements of flagellar energetics indicate that the ion-channel regulating cysteine-rich secretory proteins (CRISPs) may also be involved in regulating mammalian sperm motility.

cell biology↗