Abstract
Mitochondrial cristae are the main site for oxidative phosphorylation, which is critical for cellular energy production. Upon different physiological or pathological stresses, mitochondrial cristae undergo remodeling to reprogram mitochondrial function. However, how mitochondrial cristae are formed, maintained, and remolded is still largely unknown due to the technical challenges of tracking mitochondrial crista dynamics in living cells. Here, using live-cell Hessian structured illumination microscopy combined with transmission electron microscopy, focused ion beam/scanning electron microscopy, and three-dimensional tomographic reconstruction, we show, in living cells, that mitochondrial cristae are highly dynamic and undergo morphological changes, including elongation, shortening, fusion, division, and detachment from the mitochondrial inner boundary membrane (IBM). In addition, we find that OPA1, Yme1L, MICOS, and Sam50, along with the newly identified crista regulator ATAD3A, control mitochondrial crista dynamics. Furthermore, we discover two new types of mitochondrial crista in dysfunctional mitochondria, “cut-through crista” and “spherical crista”, which are formed due to incomplete mitochondrial fusion and dysfunction of the MICOS complex. Interestingly, cut-through crista can convert to “lamellar crista”. Overall, we provide a direct link between mitochondrial crista formation and mitochondrial crista dynamics.
Highlights
IntroductionThe inner mitochondrial membrane is organized in two morphologically distinct regions: the inner boundary membrane (IBM) and the crista membrane (CM)[1]
We used Hessian-SIM combined with transmission electron microscopy (TEM), focused ion beam/scanning electron microscopy (FIB-SEM), and 3D tomographic reconstruction to analyze the dynamic changes in mitochondrial cristae and to study the role of the related factors in regulating mitochondrial crista shape, quantity, arrangement, and distribution
The mitochondrial cristae constantly altered their lengths by elongation or shortening, detached from the inner boundary membrane (IBM), or contacted and fused with the IBM (Fig. 1A–C and S1D), suggesting that mitochondrial cristae are dynamically altered in length and constantly contact and communicate with the IBM
Summary
The inner mitochondrial membrane is organized in two morphologically distinct regions: the inner boundary membrane (IBM) and the crista membrane (CM)[1]. The IBM contains translocases and certain proteins, such as OXA1 and Mia[40], to shuttle proteins into the mitochondrial matrix[2]. The CM is usually connected to IBM by the crista junction (CJ), which is a narrow constriction[3,4]. Mitochondrial cristae have long been considered tubular or lamellar invaginations formed by protrusion of the IBM into the mitochondrial matrix.
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