Mitochondrial outer membrane permeabilization (MOMP) is often required for activation of the caspase proteases that cause apoptotic cell death. Various intermembrane space (IMS) proteins, such as cytochrome c, promote caspase activation following their mitochondrial release. As a consequence, mitochondrial outer membrane integrity is highly controlled, primarily through interactions between pro- and anti-apoptotic members of the B cell lymphoma 2 (BCL-2) protein family. Following MOMP by pro-apoptotic BCL-2-associated X protein (BAX) or BCL-2 antagonist or killer (BAK), additional regulatory mechanisms govern the mitochondrial release of IMS proteins and caspase activity. MOMP typically leads to cell death irrespective of caspase activity by causing a progressive decline in mitochondrial function, although cells can survive this under certain circumstances, which may have pathophysiological consequences.

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Mitochondria and cell death: outer membrane permeabilization and beyond

Through their many and varied metabolic functions, mitochondria power life. Paradoxically, mitochondria also have a central role in apoptotic cell death. Upon induction of mitochondrial apoptosis, mitochondrial outer membrane permeabilization (MOMP) usually commits a cell to die. Apoptotic signalling downstream of MOMP involves cytochrome c release from mitochondria and subsequent caspase activation. As such, targeting MOMP in order to manipulate cell death holds tremendous therapeutic potential across different diseases, including neurodegenerative diseases, autoimmune disorders and cancer. In this Review, we discuss new insights into how mitochondria regulate apoptotic cell death. Surprisingly, recent data demonstrate that besides eliciting caspase activation, MOMP engages various pro-inflammatory signalling functions. As we highlight, together with new findings demonstrating cell survival following MOMP, this pro-inflammatory role suggests that mitochondria-derived signalling downstream of pro-apoptotic cues may also have non-lethal functions. Finally, we discuss the importance and roles of mitochondria in other forms of regulated cell death, including necroptosis, ferroptosis and pyroptosis. Collectively, these new findings offer exciting, unexplored opportunities to target mitochondrial regulation of cell death for clinical benefit.

Mitochondria as multifaceted regulators of cell death.

Women and Human Development. Martha C. Nussbaum. New York: Cambridge University Press, 2000, 303 pp.

Women and Human Development.

A matter of life and death.

Apoptosis has been causally linked to the pathogenesis of myocardial infarction and heart failure in rodent models. This death process is mediated by two central pathways, an extrinsic pathway involving cell surface receptors and an intrinsic pathway using mitochondria and the endoplasmic reticulum. Each of these pathways has been implicated in myocardial pathology. In this review, we summarize recent advances in the understanding of the intrinsic pathway and how it relates to cardiac myocyte death and heart disease.

The Mitochondrial Death Pathway and Cardiac Myocyte Apoptosis

In sympathetic neurons, unlike most nonneuronal cells, growth factor withdrawal-induced apoptosis requires the development of competence in addition to cytochrome c release to activate caspases. Thus, although most nonneuronal cells die rapidly with cytosolic cytochrome c alone, sympathetic neurons are remarkably resistant unless they develop competence. We have identified endogenous X-linked inhibitor of apoptosis protein (XIAP) as the essential postcytochrome c regulator of caspase activation in these neurons. In contrast to wild-type neurons that are resistant to injection of cytochrome c, XIAP-deficient neurons died rapidly with cytosolic cytochrome c alone. Surprisingly, the release of endogenous Smac was not sufficient to overcome the XIAP resistance in sympathetic neurons. In contrast, the neuronal competence pathway permitted cytochrome c to activate caspases by inducing a marked reduction in XIAP levels in these neurons. Thus, the removal of XIAP inhibition appears both necessary and sufficient for cytochrome c to activate caspases in sympathetic neurons. These data identify a critical function of endogenous XIAP in regulating apoptosis in mammalian cells.

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Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis

In this article, the gender and development paradigm is critically reviewed and an alternative framework of research –identities of women– is proposed. This article contends that the gender and development paradigm is primarily guided by the tenets of Western feminisms and economic development. The article also highlights other limitations of the paradigm, including its preoccupation with male–female inequalities, macro generalisations and symbolic representation of women and a limited inclusion of local contexts. The identities of women framework proposes to address the limitations of the gender and development paradigm by studying women's conception of their environment and women's understanding of their relationship with these environments. The identities of women framework is informed by poststructuralist critique of feminism, cultural anthropology and a socio-psychological approach to identity.

Deconstructing ‘gender and development’ for ‘identities of women’

This article reports on the importance of context and culture in designing assessment tools. It does so by examining the concept of women’s autonomy in rural India. And, in exploring this issue, the article opens a dialogue on the need for newer and more grounded concepts in working with women in rural India rather than simply applying those developed in other countries or available through the international literature.

Women’s autonomy in rural India: Need for culture and context

Current social work education in India reflects globalization priorities and tendencies of neo-colonialism that emulate curriculum priorities and duplicate content developed in countries like the USA. Social work education as implemented by countries like the USA, has limited success in transnational training of social workers and their ability to address emerging social problems and deep rooted structural imbalances within non-USA social contexts. Yet, the concept of the world being an emerging global village is used to justify and reaffirm the colonial goals of universal education and pedagogies within social work and its application to starkly different contexts, such as India. This paper argues against the imperialist nature of social work education through examples from social work syllabi from Indian schools of social work. Secondly, this paper examines the role of academic collaborations and international organizations in addressing the challenges in curriculum development. Finally, through an exam...

Predicting India's Future: Does it Justify the Exportation of US Social Work Education?

Women's work in developing economies, such as India, does not necessarily present an opportunity to fight poverty. On the contrary, though women are contributing enormously to the social and economic product at national and global levels, they remain at the bottom in the hierarchy of power and rewards in the work place. The primary thesis of this article is that there is a need to examine women's association with work beginning from the point of accessing work to its outcome on women's well-being and identity. The article proposes examining work as a key variable in place of gender, while undertaking examination of women and work relationships across occupational sectors. In doing so, the article reinforces the need to identify the right research questions to address issues of structural inequality and divergence in outcomes for working women's well-being.

Shweta Singh

Papers

Critical function of endogenous XIAP in regulating caspase activation during sympathetic neuronal apoptosis

Deconstructing ‘gender and development’ for ‘identities of women’

Women’s autonomy in rural India: Need for culture and context

Predicting India's Future: Does it Justify the Exportation of US Social Work Education?

Debating Outcomes for “Working” Women: Illustrations from India